rs1494961

Variant names:

• chr4-83453327-C-G
• rs1494961
• NM_133636.5:c.916G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-83453327-C-G
• chr4-83453327-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133636.5(HELQ):​c.916G>C​(p.Val306Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V306I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 106 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05819586).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.916G>C	p.Val306Leu	missense	Exon 2 of 18	NP_598375.3
	HELQ	NM_001297755.2		c.916G>C	p.Val306Leu	missense	Exon 2 of 17	NP_001284684.2
	HELQ	NM_001297759.2		c.916G>C	p.Val306Leu	missense	Exon 2 of 2	NP_001284688.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.916G>C	p.Val306Leu	missense	Exon 2 of 18	ENSP00000295488.3
	HELQ	ENST00000510985.1	TSL:1	c.916G>C	p.Val306Leu	missense	Exon 2 of 17	ENSP00000424539.1
	HELQ	ENST00000508591.5	TSL:1	n.916G>C		non_coding_transcript_exon	Exon 2 of 17	ENSP00000424186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		2.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.063
Sift	Benign	0.19	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.054
MutPred		0.55		Loss of methylation at K303 (P = 0.0538)
MVP		0.49
MPC		0.10
ClinPred		0.26	T
GERP RS		2.3
Varity_R		0.026
gMVP		0.18
Mutation Taster		=100/0	polymorphism

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: rs1494961; hg19: chr4-84374480;