Variant 4-83427612-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_133636.5(HELQ):c.2627A>T(p.Tyr876Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,604,092 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 26 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 8.00

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 -9 ACMG points.

BP6

Variant 4-83427612-T-A is Benign according to our data. Variant chr4-83427612-T-A is described in ClinVar as [Benign]. Clinvar id is 3038702.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1769/152302) while in subpopulation AFR AF= 0.0408 (1696/41566). AF 95% confidence interval is 0.0392. There are 29 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5 link	c.2627A>T	p.Tyr876Phe	missense_variant	Exon 13 of 18	ENST00000295488.8	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2 link	c.2426A>T	p.Tyr809Phe	missense_variant	Exon 12 of 17		NP_001284684.2
HELQ	NM_001297756.2 link	c.1136A>T	p.Tyr379Phe	missense_variant	Exon 13 of 18		NP_001284685.1
HELQ	NM_001297757.2 link	c.995A>T	p.Tyr332Phe	missense_variant	Exon 12 of 17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8 link	c.2627A>T	p.Tyr876Phe	missense_variant	Exon 13 of 18	1	NM_133636.5	ENSP00000295488.3		Q8TDG4-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1753

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00295

AC:

713

AN:

241480

Hom.:

AF XY:

0.00192

AC XY:

251

AN XY:

130856

show subpopulations

Gnomad AFR exome

AF:

0.0420

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.00113

AC:

1636

AN:

1451790

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

709

AN XY:

722184

show subpopulations

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.0116

AC:

1769

AN:

152302

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

835

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000499

Hom.:

Bravo

AF:

0.0132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0429

AC:

189

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00371

AC:

450

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HELQ-related disorder

Benign:1

Mar 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

T;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.28

Sift

Benign

0.18

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.40

B;D

Vest4

0.65

MVP

0.81

MPC

0.13

ClinPred

0.042

GERP RS

5.6

Varity_R

0.34

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -17

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