Variant rs4251689 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004260.4(RECQL4):c.1258+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,610,022 control chromosomes in the GnomAD database, including 175,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13513 hom., cov: 34)

Exomes 𝑓: 0.47 ( 161818 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.296

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=-0.78).

BP6

Variant 8-144515746-C-T is Benign according to our data. Variant chr8-144515746-C-T is described in ClinVar as [Benign]. Clinvar id is 94884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515746-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 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.1258+18G>A		intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
RECQL4	ENST00000617875.6 linkuse as main transcript	c.1258+18G>A	intron_variant	1	NM_004260.4	P1
RECQL4	ENST00000621189.4 linkuse as main transcript	c.187+18G>A	intron_variant	1
RECQL4	ENST00000532846.2 linkuse as main transcript	c.143+18G>A	intron_variant	5
RECQL4	ENST00000688394.1 linkuse as main transcript		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60246

AN:

152020

Hom.:

13508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.427

GnomAD3 exomes

AF:

0.475

AC:

115771

AN:

243622

Hom.:

28477

AF XY:

0.480

AC XY:

63769

AN XY:

132750

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.464

GnomAD4 exome

AF:

0.467

AC:

680732

AN:

1457884

Hom.:

161818

Cov.:

AF XY:

0.471

AC XY:

341381

AN XY:

724960

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.548

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.396

AC:

60267

AN:

152138

Hom.:

13513

Cov.:

AF XY:

0.403

AC XY:

29989

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.581

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.463

Hom.:

18879

Bravo

AF:

0.385

Asia WGS

AF:

0.540

AC:

1877

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	-	- -

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.4

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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