4-83448938-A-G

Variant names:

• chr4-83448938-A-G
• rs13141136
• NM_133636.5:c.1036T>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.1036T>C​(p.Leu346Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,598,946 control chromosomes in the GnomAD database, including 141,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (11251 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129996 hom.)
• Consequence: HELQ NM_133636.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0370
• Publications: 23 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=-0.69).
• BP6: Variant 4-83448938-A-G is Benign according to our data. Variant chr4-83448938-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060320.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.037 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.1036T>C	p.Leu346Leu	synonymous	Exon 3 of 18	NP_598375.3
	HELQ	NM_001297756.2		c.-469T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	NP_001284685.1
	HELQ	NM_001297757.2		c.-499T>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 17	NP_001284686.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.1036T>C	p.Leu346Leu	synonymous	Exon 3 of 18	ENSP00000295488.3
	HELQ	ENST00000510985.1	TSL:1	c.1036T>C	p.Leu346Leu	synonymous	Exon 3 of 17	ENSP00000424539.1
	HELQ	ENST00000508591.5	TSL:1	n.1036T>C		non_coding_transcript_exon	Exon 3 of 17	ENSP00000424186.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53795 AN: 151628 Hom.: 11233 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.443 AC: 108724 AN: 245460 AF XY: 0.439

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.667

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.416 AC: 601529 AN: 1447202 Hom.: 129996 Cov.: 31 AF XY: 0.417 AC XY: 300202 AN XY: 720004

African (AFR) AF: 0.133 AC: 4414 AN: 33102

American (AMR) AF: 0.588 AC: 25914 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7474 AN: 25960

East Asian (EAS) AF: 0.641 AC: 25352 AN: 39548

South Asian (SAS) AF: 0.467 AC: 39604 AN: 84892

European-Finnish (FIN) AF: 0.465 AC: 24774 AN: 53290

Middle Eastern (MID) AF: 0.298 AC: 1707 AN: 5736

European-Non Finnish (NFE) AF: 0.407 AC: 447918 AN: 1100720

Other (OTH) AF: 0.407 AC: 24372 AN: 59848

GnomAD4 genome AF: 0.355 AC: 53831 AN: 151744 Hom.: 11251 Cov.: 31 AF XY: 0.364 AC XY: 26965 AN XY: 74156

African (AFR) AF: 0.151 AC: 6251 AN: 41302

American (AMR) AF: 0.470 AC: 7175 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3470

East Asian (EAS) AF: 0.665 AC: 3431 AN: 5162

South Asian (SAS) AF: 0.491 AC: 2359 AN: 4802

European-Finnish (FIN) AF: 0.454 AC: 4757 AN: 10488

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27715 AN: 67944

Other (OTH) AF: 0.342 AC: 720 AN: 2104

Alfa AF: 0.367 Hom.: 18520

Bravo AF: 0.345

Asia WGS AF: 0.577 AC: 2002 AN: 3474

ClinVar

ClinVar submissions as Germline

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	-0.69
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.037
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: rs13141136; hg19: chr4-84370091; COSMIC: COSV55026645; COSMIC: COSV55026645;