rs2024125

chr7-43118878-G-Achr7-43118878-G-C

Variant summary

Our verdict is Benign. Variant got -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

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)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HECW1	NM_015052.5	c.-32+4487G>A		intron_variant		ENST00000395891.7
HECW1-IT1	NR_135295.1	n.681-69G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW1	ENST00000395891.7	c.-32+4487G>A		intron_variant		1	NM_015052.5	P2
HECW1-IT1	ENST00000322220.1	n.681-69G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 FIN exome AF: 0.500

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

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.519

Alfa AF: 0.487 Hom.: 19401

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

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: rs2024125; hg19: chr7-43158477;