4-83452469-A-G

Variant names:

• chr4-83452469-A-G
• rs4693089
• NM_133636.5:c.1012+762T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297759.2(HELQ):​c.*712T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,016 control chromosomes in the GnomAD database, including 28,227 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 0.59 (28227 hom., cov: 32)
• Consequence: HELQ NM_001297759.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 45 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297759.2. 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.1012+762T>C		intron	N/A	NP_598375.3	Q8TDG4-1
	HELQ	NM_001297759.2		c.*712T>C		3_prime_UTR	Exon 2 of 2	NP_001284688.2
	HELQ	NM_001297758.2		c.*712T>C		3_prime_UTR	Exon 2 of 2	NP_001284687.2	Q8TDG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.1012+762T>C		intron	N/A	ENSP00000295488.3	Q8TDG4-1
	HELQ	ENST00000510985.1	TSL:1	c.1012+762T>C		intron	N/A	ENSP00000424539.1	E3W980
	HELQ	ENST00000508591.5	TSL:1	n.1012+762T>C		intron	N/A	ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90321 AN: 151898 Hom.: 28173 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90441 AN: 152016 Hom.: 28227 Cov.: 32 AF XY: 0.597 AC XY: 44388 AN XY: 74332

African (AFR) AF: 0.775 AC: 32165 AN: 41482

American (AMR) AF: 0.607 AC: 9250 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3453 AN: 5180

South Asian (SAS) AF: 0.614 AC: 2963 AN: 4826

European-Finnish (FIN) AF: 0.510 AC: 5373 AN: 10542

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33887 AN: 67954

Other (OTH) AF: 0.548 AC: 1157 AN: 2112

Alfa AF: 0.530 Hom.: 45600

Bravo AF: 0.605

Asia WGS AF: 0.681 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.81
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: rs4693089; hg19: chr4-84373622;