rs948891282

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.114C>T(p.Thr38Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,100 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. T38T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.563

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=-0.61).

BP6

Variant 8-144517606-G-A is Benign according to our data. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517606-G-A is described in CliVar as Likely_benign. Clinvar id is 459306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.563 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.114C>T	p.Thr38Thr	synonymous_variant	Exon 2 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.114C>T	p.Thr38Thr	synonymous_variant	Exon 2 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1334886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

658192

African (AFR)

AF:

0.00

AC:

AN:

26742

American (AMR)

AF:

0.00

AC:

AN:

28990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23462

East Asian (EAS)

AF:

0.00

AC:

AN:

30442

South Asian (SAS)

AF:

0.00

AC:

AN:

73918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1058702

Other (OTH)

AF:

0.00

AC:

AN:

55462

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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:

0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Nov 26, 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. -

RECQL4-related disorder

Benign:1

Feb 18, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Baller-Gerold syndrome

Benign:1

Sep 30, 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

-0.61

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.56

PromoterAI

0.16

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over