4-83432001-T-C

Variant summary

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

The NM_133636.5(HELQ):c.2190+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 559,070 control chromosomes in the GnomAD database, including 48,141 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 0.35 (11089 hom., cov: 32)
  • Exomes 𝑓: 0.42 (37052 hom.)
• Consequence: HELQ NM_133636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELQ	NM_133636.5	c.2190+125A>G		intron_variant		ENST00000295488.8
HELQ	NM_001297755.2	c.1989+125A>G		intron_variant
HELQ	NM_001297756.2	c.699+125A>G		intron_variant
HELQ	NM_001297757.2	c.558+125A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8	c.2190+125A>G		intron_variant		1	NM_133636.5	P1
HELQ	ENST00000510985.1	c.1989+125A>G		intron_variant		1
HELQ	ENST00000508591.5	c.*622+125A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52668 AN: 151768 Hom.: 11073 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.416 AC: 169515 AN: 407184 Hom.: 37052 AF XY: 0.417 AC XY: 88698 AN XY: 212596

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.347 AC: 52704 AN: 151886 Hom.: 11089 Cov.: 32 AF XY: 0.357 AC XY: 26479 AN XY: 74254

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.333

Alfa AF: 0.258 Hom.: 716

Bravo AF: 0.336

Asia WGS AF: 0.574 AC: 1975 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.21
Dann	Benign	0.82

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: rs2047210; hg19: chr4-84353154; COSMIC: COSV55026821; COSMIC: COSV55026821;