8-144512248-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004260.4(RECQL4):c.3132C>G(p.Thr1044Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 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 0.0000066 ( 0 hom., cov: 36)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-144512248-G-C is Benign according to our data. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144512248-G-C is described in CliVar as Likely_benign. Clinvar id is 1574097.Status of the report is criteria_provided_single_submitter, 1 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>G	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>G	p.Thr1044Thr	synonymous_variant	Exon 18 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460138

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726344

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

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:

0.00

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:

0.00

AC:

AN:

1111740

Other (OTH)

AF:

0.00

AC:

AN:

60344

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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

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:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Baller-Gerold syndrome

Benign:1

Feb 20, 2023

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

-0.83

CADD

Benign

0.015

(source)

DANN

Benign

0.49

PhyloP100

-2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over