rs11099600

Positions:

• chr4-83446133-G-A
• chr4-83446133-G-T

Variant summary

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

The NM_133636.5(HELQ):​c.1393-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,263,222 control chromosomes in the GnomAD database, including 165,805 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 0.50 (19610 hom., cov: 32)
  • Exomes 𝑓: 0.51 (146195 hom.)
• Consequence: HELQ NM_133636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELQ	NM_133636.5	c.1393-47C>T		intron_variant		ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2	c.1192-47C>T		intron_variant			NP_001284684.2
HELQ	NM_001297756.2	c.-112-47C>T		intron_variant			NP_001284685.1
HELQ	NM_001297757.2	c.-142-47C>T		intron_variant			NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.1393-47C>T		intron_variant		1	NM_133636.5	ENSP00000295488	P1
HELQ	ENST00000510985.1	c.1192-47C>T		intron_variant		1		ENSP00000424539
HELQ	ENST00000508591.5	c.1393-47C>T		intron_variant, NMD_transcript_variant		1		ENSP00000424186

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76345 AN: 151682 Hom.: 19572 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.474

GnomAD3 exomes AF: 0.539 AC: 131808 AN: 244660 Hom.: 36237 AF XY: 0.536 AC XY: 71045 AN XY: 132454

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.667

Gnomad SAS exome AF: 0.595

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.508 AC: 564255 AN: 1111422 Hom.: 146195 Cov.: 15 AF XY: 0.510 AC XY: 290537 AN XY: 569176

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.504 AC: 76438 AN: 151800 Hom.: 19610 Cov.: 32 AF XY: 0.510 AC XY: 37800 AN XY: 74158

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.477

Alfa AF: 0.504 Hom.: 3617

Bravo AF: 0.501

Asia WGS AF: 0.660 AC: 2290 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.42

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: rs11099600; hg19: chr4-84367286;