Variant 4-83426090-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_133636.5(HELQ):c.2679T>C(p.Phe893=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,564,474 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 8 hom. )

Consequence

HELQ
NM_133636.5 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0240

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 -11 ACMG points.

BP4

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

BP6

Variant 4-83426090-A-G is Benign according to our data. Variant chr4-83426090-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654856.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELQ	NM_133636.5 linkuse as main transcript	c.2679T>C	p.Phe893=	splice_region_variant, synonymous_variant	14/18	ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2 linkuse as main transcript	c.2478T>C	p.Phe826=	splice_region_variant, synonymous_variant	13/17		NP_001284684.2
HELQ	NM_001297756.2 linkuse as main transcript	c.1188T>C	p.Phe396=	splice_region_variant, synonymous_variant	14/18		NP_001284685.1
HELQ	NM_001297757.2 linkuse as main transcript	c.1047T>C	p.Phe349=	splice_region_variant, synonymous_variant	13/17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2679T>C	p.Phe893=	splice_region_variant, synonymous_variant	14/18	1	NM_133636.5	ENSP00000295488	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.2478T>C	p.Phe826=	splice_region_variant, synonymous_variant	13/17	1		ENSP00000424539
HELQ	ENST00000508591.5 linkuse as main transcript	c.*1111T>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	13/17	1		ENSP00000424186
HELQ	ENST00000512539.1 linkuse as main transcript	n.167T>C		splice_region_variant, non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

306

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00161

AC:

390

AN:

242468

Hom.:

AF XY:

0.00167

AC XY:

218

AN XY:

130892

show subpopulations

Gnomad AFR exome

AF:

0.000377

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000527

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00254

AC:

3585

AN:

1412138

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1810

AN XY:

704200

show subpopulations

Gnomad4 AFR exome

AF:

0.000433

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000507

Gnomad4 FIN exome

AF:

0.000904

Gnomad4 NFE exome

AF:

0.00311

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00201

AC:

306

AN:

152336

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00202

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

HELQ: BP4, BP7 -

HELQ-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2019

This variant is classified as likely 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

-0.81

CADD

Benign

0.55

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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