rs2306386

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004260.4(RECQL4):c.132A>G(p.Glu44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,591,644 control chromosomes in the GnomAD database, including 213,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23183 hom., cov: 35)

Exomes 𝑓: 0.51 ( 189901 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.186

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 8-144517495-T-C is Benign according to our data. Variant chr8-144517495-T-C is described in ClinVar as [Benign]. Clinvar id is 94885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517495-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.186 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.132A>G	p.Glu44=	synonymous_variant	3/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.132A>G	p.Glu44=	synonymous_variant	3/21	1	NM_004260.4	P1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83323

AN:

151950

Hom.:

23153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.546

GnomAD3 exomes

AF:

0.537

AC:

112047

AN:

208800

Hom.:

30572

AF XY:

0.534

AC XY:

61976

AN XY:

116114

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.486

Gnomad SAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.511

AC:

735776

AN:

1439580

Hom.:

189901

Cov.:

AF XY:

0.513

AC XY:

367242

AN XY:

715246

show subpopulations

Gnomad4 AFR exome

AF:

0.620

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.548

AC:

83407

AN:

152064

Hom.:

23183

Cov.:

AF XY:

0.554

AC XY:

41184

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.470

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.517

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.530

Hom.:

8370

Bravo

AF:

0.557

Asia WGS

AF:

0.606

AC:

2107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -

Rothmund-Thomson syndrome type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Baller-Gerold syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Rapadilino syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

7.4

Dann

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over