4-83443598-A-T

Variant names:

• chr4-83443598-A-T
• rs7665103
• NM_133636.5:c.1482T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133636.5(HELQ):​c.1482T>A​(p.Ile494Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HELQ NM_133636.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5	c.1482T>A	p.Ile494Ile	synonymous_variant	Exon 6 of 18	ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2	c.1281T>A	p.Ile427Ile	synonymous_variant	Exon 5 of 17		NP_001284684.2
HELQ	NM_001297756.2	c.-23T>A		5_prime_UTR_variant	Exon 6 of 18		NP_001284685.1
HELQ	NM_001297757.2	c.-69-2195T>A		intron_variant	Intron 5 of 16		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.1482T>A	p.Ile494Ile	synonymous_variant	Exon 6 of 18	1	NM_133636.5	ENSP00000295488.3
HELQ	ENST00000510985.1	c.1281T>A	p.Ile427Ile	synonymous_variant	Exon 5 of 17	1		ENSP00000424539.1
HELQ	ENST00000508591.5	n.1466-2195T>A		intron_variant	Intron 5 of 16	1		ENSP00000424186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382128 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 689962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.7
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7665103; hg19: chr4-84364751;