dbSNP rs7665103: HELQ:p.Ile494Ile (chr4-83443598-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_133636.5(HELQ):c.1482T>C(p.Ile494Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,524,536 control chromosomes in the GnomAD database, including 137,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.44 ( 15189 hom., cov: 32)

Exomes 𝑓: 0.41 ( 122226 hom. )

Consequence

HELQ
NM_133636.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.66

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 4-83443598-A-G is Benign according to our data. Variant chr4-83443598-A-G is described in ClinVar as [Benign]. Clinvar id is 3059382.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5 link	c.1482T>C	p.Ile494Ile	synonymous_variant	Exon 6 of 18	ENST00000295488.8	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2 link	c.1281T>C	p.Ile427Ile	synonymous_variant	Exon 5 of 17		NP_001284684.2
HELQ	NM_001297756.2 link	c.-23T>C		5_prime_UTR_variant	Exon 6 of 18		NP_001284685.1
HELQ	NM_001297757.2 link	c.-69-2195T>C		intron_variant	Intron 5 of 16		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HELQ	ENST00000295488.8 link	c.1482T>C	p.Ile494Ile	synonymous_variant	Exon 6 of 18	1	NM_133636.5	ENSP00000295488.3	Q8TDG4-1
HELQ	ENST00000510985.1 link	c.1281T>C	p.Ile427Ile	synonymous_variant	Exon 5 of 17	1		ENSP00000424539.1	E3W980
HELQ	ENST00000508591.5 link	n.1466-2195T>C		intron_variant	Intron 5 of 16	1		ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66697

AN:

151872

Hom.:

15163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.666

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.456

AC:

106435

AN:

233522

Hom.:

25526

AF XY:

0.446

AC XY:

56359

AN XY:

126258

show subpopulations

Gnomad AFR exome

AF:

0.439

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.662

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.462

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.415

AC:

569357

AN:

1372546

Hom.:

122226

Cov.:

AF XY:

0.415

AC XY:

284714

AN XY:

685400

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.639

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.464

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.439

AC:

66775

AN:

151990

Hom.:

15189

Cov.:

AF XY:

0.446

AC XY:

33096

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.666

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.402

Hom.:

16294

Bravo

AF:

0.440

Asia WGS

AF:

0.603

AC:

2096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HELQ-related disorder

Benign:1

Oct 21, 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

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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