chr4-83407479-C-T

Position:

• chr4-83407479-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133636.5(HELQ):​c.3280G>A​(p.Val1094Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,607,490 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.031 (255 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (236 hom.)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040671825).
• BP6: Variant 4-83407479-C-T is Benign according to our data. Variant chr4-83407479-C-T is described in ClinVar as [Benign]. Clinvar id is 3037625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELQ	NM_133636.5	c.3280G>A	p.Val1094Met	missense_variant	18/18	ENST00000295488.8
HELQ	NM_001297755.2	c.3079G>A	p.Val1027Met	missense_variant	17/17
HELQ	NM_001297756.2	c.1789G>A	p.Val597Met	missense_variant	18/18
HELQ	NM_001297757.2	c.1648G>A	p.Val550Met	missense_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8	c.3280G>A	p.Val1094Met	missense_variant	18/18	1	NM_133636.5	P1
HELQ	ENST00000510985.1	c.3079G>A	p.Val1027Met	missense_variant	17/17	1
HELQ	ENST00000508591.5	c.*1712G>A		3_prime_UTR_variant, NMD_transcript_variant	17/17	1
HELQ	ENST00000512539.1	n.519G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4698 AN: 152182 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000602

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00813 AC: 1992 AN: 244962 Hom.: 99 AF XY: 0.00596 AC XY: 790 AN XY: 132628

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00551

Gnomad ASJ exome AF: 0.000500

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000442

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000500

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.00339 AC: 4926 AN: 1455190 Hom.: 236 Cov.: 29 AF XY: 0.00300 AC XY: 2174 AN XY: 723814

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.00659

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000519

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000424

Gnomad4 OTH exome AF: 0.00805

GnomAD4 genome AF: 0.0310 AC: 4722 AN: 152300 Hom.: 255 Cov.: 32 AF XY: 0.0300 AC XY: 2233 AN XY: 74470

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00565 Hom.: 92

Bravo AF: 0.0345

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.111 AC: 489

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0102 AC: 1239

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000554

EpiControl AF: 0.000963

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HELQ-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 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
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.9
DANN	Benign	0.88
DEOGEN2	Benign	0.00057	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.080
Sift	Benign	0.19	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.063
MPC		0.11
ClinPred		0.0077	T
GERP RS		0.38
Varity_R		0.034
gMVP		0.22

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

Other links and lift over

dbSNP: rs17006794; hg19: chr4-84328632;