4-83452469-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133636.5(HELQ):c.1012+762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,016 control chromosomes in the GnomAD database, including 28,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28227 hom., cov: 32)
• Consequence: HELQ NM_133636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELQ	NM_133636.5	c.1012+762T>C		intron_variant		ENST00000295488.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8	c.1012+762T>C		intron_variant		1	NM_133636.5	P1
HELQ	ENST00000510985.1	c.1012+762T>C		intron_variant		1
HELQ	ENST00000508591.5	c.1012+762T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90321 AN: 151898 Hom.: 28173 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90441 AN: 152016 Hom.: 28227 Cov.: 32 AF XY: 0.597 AC XY: 44388 AN XY: 74332

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.548

Alfa AF: 0.511 Hom.: 15286

Bravo AF: 0.605

Asia WGS AF: 0.681 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.7
Dann	Benign	0.63

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: rs4693089; hg19: chr4-84373622;