4-83448938-A-G

Variant names:

• chr4-83448938-A-G
• rs13141136
• NM_133636.5:c.1036T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001297756.2(HELQ):​c.-469T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,598,946 control chromosomes in the GnomAD database, including 141,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (11251 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129996 hom.)
• Consequence: HELQ NM_001297756.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0370

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 4-83448938-A-G is Benign according to our data. Variant chr4-83448938-A-G is described in ClinVar as [Benign]. Clinvar id is 3060320.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5	c.1036T>C	p.Leu346Leu	synonymous_variant	Exon 3 of 18	ENST00000295488.8	NP_598375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.1036T>C	p.Leu346Leu	synonymous_variant	Exon 3 of 18	1	NM_133636.5	ENSP00000295488.3
HELQ	ENST00000510985.1	c.1036T>C	p.Leu346Leu	synonymous_variant	Exon 3 of 17	1		ENSP00000424539.1
HELQ	ENST00000508591.5	n.1036T>C		non_coding_transcript_exon_variant	Exon 3 of 17	1		ENSP00000424186.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53795 AN: 151628 Hom.: 11233 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.337

GnomAD3 exomes AF: 0.443 AC: 108724 AN: 245460 Hom.: 26021 AF XY: 0.439 AC XY: 58332 AN XY: 132816

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.667

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.416 AC: 601529 AN: 1447202 Hom.: 129996 Cov.: 31 AF XY: 0.417 AC XY: 300202 AN XY: 720004

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.355 AC: 53831 AN: 151744 Hom.: 11251 Cov.: 31 AF XY: 0.364 AC XY: 26965 AN XY: 74156

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.342

Alfa AF: 0.382 Hom.: 15072

Bravo AF: 0.345

Asia WGS AF: 0.577 AC: 2002 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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	-0.69
CADD	Benign	2.8
DANN	Benign	0.75

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: rs13141136; hg19: chr4-84370091; COSMIC: COSV55026645; COSMIC: COSV55026645;