rs4244610

Positions:

chr8-144512131-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.3236+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,599,570 control chromosomes in the GnomAD database, including 177,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14483 hom., cov: 35)

Exomes 𝑓: 0.47 ( 163048 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-144512131-G-A is Benign according to our data. Variant chr8-144512131-G-A is described in ClinVar as [Benign]. Clinvar id is 94893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512131-G-A is described in Lovd as [Benign]. Variant chr8-144512131-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 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.3236+13C>T		intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.3236+13C>T		intron_variant		1	NM_004260.4	P1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63981

AN:

152070

Hom.:

14478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.453

GnomAD3 exomes

AF:

0.490

AC:

112458

AN:

229620

Hom.:

28014

AF XY:

0.493

AC XY:

62073

AN XY:

125874

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.570

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.479

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.472

AC:

682849

AN:

1447382

Hom.:

163048

Cov.:

AF XY:

0.476

AC XY:

341743

AN XY:

718472

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.565

Gnomad4 FIN exome

AF:

0.496

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.421

AC:

64001

AN:

152188

Hom.:

14483

Cov.:

AF XY:

0.427

AC XY:

31765

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.499

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.444

Hom.:

2851

Bravo

AF:

0.414

Asia WGS

AF:

0.534

AC:

1856

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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)	May 08, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Baller-Gerold syndrome

Benign:2

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

Rapadilino syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

- -

Rothmund-Thomson syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.094

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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