Variant rs13141136 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_133636.5(HELQ):c.1036T>C(p.Leu346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,598,946 control chromosomes in the GnomAD database, including 141,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 11251 hom., cov: 31)

Exomes 𝑓: 0.42 ( 129996 hom. )

Consequence

HELQ
NM_133636.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0370

Variant links:

Genes affected

HELQ (HGNC:18536): (helicase, POLQ like) HEL308 is a single-stranded DNA-dependent ATPase and DNA helicase (Marini and Wood, 2002 [PubMed 11751861]).[supplied by OMIM, Mar 2008]

HELQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 4-83448938-A-G is Benign according to our data. Variant chr4-83448938-A-G is described in ClinVar as [Benign]. Clinvar id is 3060320.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.037 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HELQ	NM_133636.5 linkuse as main transcript	c.1036T>C	p.Leu346=	synonymous_variant	3/18	ENST00000295488.8
HELQ	NM_001297755.2 linkuse as main transcript	c.1036T>C	p.Leu346=	synonymous_variant	3/17
HELQ	NM_001297756.2 linkuse as main transcript	c.-469T>C		5_prime_UTR_variant	3/18
HELQ	NM_001297757.2 linkuse as main transcript	c.-499T>C		5_prime_UTR_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.1036T>C	p.Leu346=	synonymous_variant	3/18	1	NM_133636.5	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.1036T>C	p.Leu346=	synonymous_variant	3/17	1
HELQ	ENST00000508591.5 linkuse as main transcript	c.1036T>C	p.Leu346=	synonymous_variant, NMD_transcript_variant	3/17	1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53795

AN:

151628

Hom.:

11233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.443

AC:

108724

AN:

245460

Hom.:

26021

AF XY:

0.439

AC XY:

58332

AN XY:

132816

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.667

Gnomad SAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.463

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.416

AC:

601529

AN:

1447202

Hom.:

129996

Cov.:

AF XY:

0.417

AC XY:

300202

AN XY:

720004

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.588

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.641

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.407

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.355

AC:

53831

AN:

151744

Hom.:

11251

Cov.:

AF XY:

0.364

AC XY:

26965

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.665

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.382

Hom.:

15072

Bravo

AF:

0.345

Asia WGS

AF:

0.577

AC:

2002

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HELQ-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.8

DANN

Benign

0.75

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