chr4-83453327-C-T

Variant names:

• chr4-83453327-C-T
• rs1494961
• NM_133636.5:c.916G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_133636.5(HELQ):​c.916G>A​(p.Val306Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,612,154 control chromosomes in the GnomAD database, including 227,195 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (28233 hom., cov: 32)
  • Exomes 𝑓: 0.52 (198962 hom.)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.42
• Publications: 106 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.8009475E-7).
• BP6: Variant 4-83453327-C-T is Benign according to our data. Variant chr4-83453327-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060988.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.916G>A	p.Val306Ile	missense	Exon 2 of 18	NP_598375.3
	HELQ	NM_001297755.2		c.916G>A	p.Val306Ile	missense	Exon 2 of 17	NP_001284684.2
	HELQ	NM_001297759.2		c.916G>A	p.Val306Ile	missense	Exon 2 of 2	NP_001284688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.916G>A	p.Val306Ile	missense	Exon 2 of 18	ENSP00000295488.3
	HELQ	ENST00000510985.1	TSL:1	c.916G>A	p.Val306Ile	missense	Exon 2 of 17	ENSP00000424539.1
	HELQ	ENST00000508591.5	TSL:1	n.916G>A		non_coding_transcript_exon	Exon 2 of 17	ENSP00000424186.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90350 AN: 151946 Hom.: 28179 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.546

GnomAD2 exomes AF: 0.563 AC: 141150 AN: 250682 AF XY: 0.554

Gnomad AFR exome AF: 0.777

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.667

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.517 AC: 755413 AN: 1460090 Hom.: 198962 Cov.: 36 AF XY: 0.518 AC XY: 376597 AN XY: 726442

African (AFR) AF: 0.793 AC: 26503 AN: 33428

American (AMR) AF: 0.670 AC: 29862 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11816 AN: 26078

East Asian (EAS) AF: 0.641 AC: 25442 AN: 39680

South Asian (SAS) AF: 0.594 AC: 51094 AN: 86038

European-Finnish (FIN) AF: 0.519 AC: 27711 AN: 53404

Middle Eastern (MID) AF: 0.496 AC: 2853 AN: 5756

European-Non Finnish (NFE) AF: 0.493 AC: 547925 AN: 1110816

Other (OTH) AF: 0.534 AC: 32207 AN: 60332

GnomAD4 genome AF: 0.595 AC: 90470 AN: 152064 Hom.: 28233 Cov.: 32 AF XY: 0.597 AC XY: 44379 AN XY: 74310

African (AFR) AF: 0.775 AC: 32158 AN: 41490

American (AMR) AF: 0.606 AC: 9262 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1543 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3462 AN: 5184

South Asian (SAS) AF: 0.614 AC: 2963 AN: 4826

European-Finnish (FIN) AF: 0.510 AC: 5381 AN: 10546

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33890 AN: 67950

Other (OTH) AF: 0.548 AC: 1156 AN: 2108

Alfa AF: 0.522 Hom.: 101421

Bravo AF: 0.605

TwinsUK AF: 0.500 AC: 1854

ALSPAC AF: 0.480 AC: 1850

ESP6500AA AF: 0.776 AC: 3420

ESP6500EA AF: 0.501 AC: 4311

ExAC AF: 0.562 AC: 68259

Asia WGS AF: 0.680 AC: 2365 AN: 3478

EpiCase AF: 0.487

EpiControl AF: 0.477

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HELQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.64
DEOGEN2	Benign	0.00057	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.056	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N
PhyloP100		2.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.080
Sift	Benign	1.0	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.084
ClinPred		0.0017	T
GERP RS		2.3
Varity_R		0.012
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1494961; hg19: chr4-84374480; COSMIC: COSV55024221; COSMIC: COSV55024221;