NM_004260.4:c.3132C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_004260.4(RECQL4):c.3132C>T(p.Thr1044Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1044T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.11

Publications

0 publications found

Variant links:

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-144512248-G-A is Benign according to our data. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512248-G-A is described in CliVar as Likely_benign. Clinvar id is 459460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.3132C>T	p.Thr1044Thr	synonymous_variant	Exon 18 of 21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.3132C>T	p.Thr1044Thr	synonymous_variant	Exon 18 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

247252

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000555

AC:

AN:

1460138

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

726344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000684

AC:

AN:

1111740

Other (OTH)

AF:

0.0000331

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Nov 22, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Baller-Gerold syndrome

Benign:1

Nov 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.086

(source)

DANN

Benign

0.68

PhyloP100

-2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over