rs2024125

Variant names:

• chr7-43118878-G-A
• rs2024125
• NM_015052.5:c.-32+4487G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-43118878-G-A
• chr7-43118878-G-C
• chr7-43118878-G-T

Variant summary

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

The NM_015052.5(HECW1):​c.-32+4487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,836 control chromosomes in the GnomAD database, including 22,675 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 0.54 (22674 hom., cov: 30)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 11 publications found

Genes affected

HECW1 (HGNC:22195): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; negative regulation of sodium ion transmembrane transporter activity; and regulation of dendrite morphogenesis. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HECW1-IT1 (HGNC:41465): (HECW1 intronic transcript 1)

ENSG00000310044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECW1	NM_015052.5	c.-32+4487G>A		intron_variant	Intron 2 of 29	ENST00000395891.7	NP_055867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECW1	ENST00000395891.7	c.-32+4487G>A		intron_variant	Intron 2 of 29	1	NM_015052.5	ENSP00000379228.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82152 AN: 151712 Hom.: 22663 Cov.: 30

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.541 AC: 82198 AN: 151832 Hom.: 22674 Cov.: 30 AF XY: 0.550 AC XY: 40780 AN XY: 74194

African (AFR) AF: 0.605 AC: 25024 AN: 41384

American (AMR) AF: 0.525 AC: 8013 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1744 AN: 3462

East Asian (EAS) AF: 0.758 AC: 3907 AN: 5152

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4810

European-Finnish (FIN) AF: 0.636 AC: 6714 AN: 10560

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32526 AN: 67888

Other (OTH) AF: 0.519 AC: 1093 AN: 2108

Alfa AF: 0.500 Hom.: 55121

Bravo AF: 0.534

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.31
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: rs2024125; hg19: chr7-43158477;