4-83431597-T-C

Position:

• chr4-83431597-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.2295+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 634,658 control chromosomes in the GnomAD database, including 56,566 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 (11168 hom., cov: 32)
  • Exomes 𝑓: 0.42 (45398 hom.)
• Consequence: HELQ NM_133636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.92).
• 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	Protein	UniProt
HELQ	NM_133636.5	c.2295+67A>G		intron_variant		ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2	c.2094+67A>G		intron_variant			NP_001284684.2
HELQ	NM_001297756.2	c.804+67A>G		intron_variant			NP_001284685.1
HELQ	NM_001297757.2	c.663+67A>G		intron_variant			NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.2295+67A>G		intron_variant		1	NM_133636.5	ENSP00000295488.3
HELQ	ENST00000510985.1	c.2094+67A>G		intron_variant		1		ENSP00000424539.1
HELQ	ENST00000508591.5	n.*727+67A>G		intron_variant		1		ENSP00000424186.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53174 AN: 151612 Hom.: 11152 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.423 AC: 204240 AN: 482928 Hom.: 45398 AF XY: 0.421 AC XY: 110371 AN XY: 261856

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.634

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.351 AC: 53211 AN: 151730 Hom.: 11168 Cov.: 32 AF XY: 0.360 AC XY: 26711 AN XY: 74168

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.335

Alfa AF: 0.383 Hom.: 1511

Bravo AF: 0.340

Asia WGS AF: 0.576 AC: 1987 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.4
DANN	Benign	0.54

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: rs12645412; hg19: chr4-84352750;