4-83443598-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. I494I) has been classified as Benign.

• 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
• Publications: 24 publications found

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

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.1482T>A	p.Ile494Ile	synonymous	Exon 6 of 18	NP_598375.3	Q8TDG4-1
	HELQ	NM_001297755.2		c.1281T>A	p.Ile427Ile	synonymous	Exon 5 of 17	NP_001284684.2	E3W980
	HELQ	NM_001297756.2		c.-23T>A		5_prime_UTR	Exon 6 of 18	NP_001284685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.1482T>A	p.Ile494Ile	synonymous	Exon 6 of 18	ENSP00000295488.3	Q8TDG4-1
	HELQ	ENST00000510985.1	TSL:1	c.1281T>A	p.Ile427Ile	synonymous	Exon 5 of 17	ENSP00000424539.1	E3W980
	HELQ	ENST00000508591.5	TSL:1	n.1466-2195T>A		intron	N/A	ENSP00000424186.1	E3W982

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

African (AFR) AF: 0.00 AC: 0 AN: 31348

American (AMR) AF: 0.00 AC: 0 AN: 39682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39004

South Asian (SAS) AF: 0.00 AC: 0 AN: 81084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050372

Other (OTH) AF: 0.00 AC: 0 AN: 57434

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.7
DANN	Benign	0.65
PhyloP100		1.7

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

Other links and lift over

dbSNP: rs7665103; hg19: chr4-84364751;