rs886550

chr7-43296644-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015052.5(HECW1):c.28-15119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,050 control chromosomes in the GnomAD database, including 5,088 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 0.23 (5088 hom., cov: 33)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECW1	NM_015052.5	c.28-15119G>T		intron_variant		ENST00000395891.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW1	ENST00000395891.7	c.28-15119G>T		intron_variant		1	NM_015052.5	P2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34475 AN: 151932 Hom.: 5079 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.227 AC: 34528 AN: 152050 Hom.: 5088 Cov.: 33 AF XY: 0.232 AC XY: 17234 AN XY: 74332

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.209

Alfa AF: 0.145 Hom.: 3998

Bravo AF: 0.248

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.2
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs886550; hg19: chr7-43336243;