4-83431597-T-C

Variant names:

• chr4-83431597-T-C
• rs12645412
• NM_133636.5:c.2295+67A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
HELQ	NM_133636.5	c.2295+67A>G		intron_variant	Intron 11 of 17	ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2	c.2094+67A>G		intron_variant	Intron 10 of 16		NP_001284684.2
HELQ	NM_001297756.2	c.804+67A>G		intron_variant	Intron 11 of 17		NP_001284685.1
HELQ	NM_001297757.2	c.663+67A>G		intron_variant	Intron 10 of 16		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.2295+67A>G		intron_variant	Intron 11 of 17	1	NM_133636.5	ENSP00000295488.3
HELQ	ENST00000510985.1	c.2094+67A>G		intron_variant	Intron 10 of 16	1		ENSP00000424539.1
HELQ	ENST00000508591.5	n.*727+67A>G		intron_variant	Intron 10 of 16	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

African (AFR) AF: 0.137 AC: 1406 AN: 10300

American (AMR) AF: 0.578 AC: 11616 AN: 20104

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 4005 AN: 14296

East Asian (EAS) AF: 0.634 AC: 16562 AN: 26138

South Asian (SAS) AF: 0.459 AC: 13665 AN: 29802

European-Finnish (FIN) AF: 0.464 AC: 19299 AN: 41558

Middle Eastern (MID) AF: 0.279 AC: 606 AN: 2174

European-Non Finnish (NFE) AF: 0.406 AC: 127365 AN: 314048

Other (OTH) AF: 0.396 AC: 9716 AN: 24508

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

African (AFR) AF: 0.140 AC: 5795 AN: 41498

American (AMR) AF: 0.467 AC: 7129 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3491 AN: 5180

South Asian (SAS) AF: 0.487 AC: 2346 AN: 4822

European-Finnish (FIN) AF: 0.455 AC: 4693 AN: 10312

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27649 AN: 67862

Other (OTH) AF: 0.335 AC: 705 AN: 2104

Alfa AF: 0.374 Hom.: 1521

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12645412; hg19: chr4-84352750;