4-83443598-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_133636.5(HELQ):​c.1482T>C​(p.Ile494Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,524,536 control chromosomes in the GnomAD database, including 137,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. I494I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.44 (15189 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122226 hom.)
• Consequence: HELQ NM_133636.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 4-83443598-A-G is Benign according to our data. Variant chr4-83443598-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059382.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

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>C	p.Ile494Ile	synonymous	Exon 6 of 18	NP_598375.3	Q8TDG4-1
	HELQ	NM_001297755.2		c.1281T>C	p.Ile427Ile	synonymous	Exon 5 of 17	NP_001284684.2	E3W980
	HELQ	NM_001297756.2		c.-23T>C		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>C	p.Ile494Ile	synonymous	Exon 6 of 18	ENSP00000295488.3	Q8TDG4-1
	HELQ	ENST00000510985.1	TSL:1	c.1281T>C	p.Ile427Ile	synonymous	Exon 5 of 17	ENSP00000424539.1	E3W980
	HELQ	ENST00000508591.5	TSL:1	n.1466-2195T>C		intron	N/A	ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66697 AN: 151872 Hom.: 15163 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.456 AC: 106435 AN: 233522 AF XY: 0.446

Gnomad AFR exome AF: 0.439

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.662

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.415 AC: 569357 AN: 1372546 Hom.: 122226 Cov.: 21 AF XY: 0.415 AC XY: 284714 AN XY: 685400

African (AFR) AF: 0.437 AC: 13620 AN: 31152

American (AMR) AF: 0.591 AC: 23360 AN: 39530

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 6565 AN: 25012

East Asian (EAS) AF: 0.639 AC: 24871 AN: 38926

South Asian (SAS) AF: 0.462 AC: 37230 AN: 80660

European-Finnish (FIN) AF: 0.464 AC: 24359 AN: 52454

Middle Eastern (MID) AF: 0.309 AC: 1700 AN: 5510

European-Non Finnish (NFE) AF: 0.397 AC: 413828 AN: 1042182

Other (OTH) AF: 0.417 AC: 23824 AN: 57120

GnomAD4 genome AF: 0.439 AC: 66775 AN: 151990 Hom.: 15189 Cov.: 32 AF XY: 0.446 AC XY: 33096 AN XY: 74272

African (AFR) AF: 0.446 AC: 18484 AN: 41432

American (AMR) AF: 0.502 AC: 7665 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3448 AN: 5180

South Asian (SAS) AF: 0.496 AC: 2395 AN: 4824

European-Finnish (FIN) AF: 0.454 AC: 4775 AN: 10518

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27784 AN: 67982

Other (OTH) AF: 0.399 AC: 840 AN: 2104

Alfa AF: 0.408 Hom.: 22090

Bravo AF: 0.440

Asia WGS AF: 0.603 AC: 2096 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HELQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.9
DANN	Benign	0.65
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV55028346;