4-83426090-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_133636.5(HELQ):c.2679T>C(p.Phe893=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,564,474 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: HELQ NM_133636.5 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-83426090-A-G is Benign according to our data. Variant chr4-83426090-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELQ	NM_133636.5	c.2679T>C	p.Phe893=	splice_region_variant, synonymous_variant	14/18	ENST00000295488.8
HELQ	NM_001297755.2	c.2478T>C	p.Phe826=	splice_region_variant, synonymous_variant	13/17
HELQ	NM_001297756.2	c.1188T>C	p.Phe396=	splice_region_variant, synonymous_variant	14/18
HELQ	NM_001297757.2	c.1047T>C	p.Phe349=	splice_region_variant, synonymous_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8	c.2679T>C	p.Phe893=	splice_region_variant, synonymous_variant	14/18	1	NM_133636.5	P1
HELQ	ENST00000510985.1	c.2478T>C	p.Phe826=	splice_region_variant, synonymous_variant	13/17	1
HELQ	ENST00000508591.5	c.*1111T>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	13/17	1
HELQ	ENST00000512539.1	n.167T>C		splice_region_variant, non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00161 AC: 390 AN: 242468 Hom.: 1 AF XY: 0.00167 AC XY: 218 AN XY: 130892

Gnomad AFR exome AF: 0.000377

Gnomad AMR exome AF: 0.000756

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000527

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.00291

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.00254 AC: 3585 AN: 1412138 Hom.: 8 Cov.: 22 AF XY: 0.00257 AC XY: 1810 AN XY: 704200

Gnomad4 AFR exome AF: 0.000433

Gnomad4 AMR exome AF: 0.000739

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000507

Gnomad4 FIN exome AF: 0.000904

Gnomad4 NFE exome AF: 0.00311

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.00169 AC XY: 126 AN XY: 74494

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00295 Hom.: 4

Bravo AF: 0.00202

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

HELQ: BP4, BP7 -

HELQ-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.55
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144287404; hg19: chr4-84347243;