7-43215011-C-A

Position:

• chr7-43215011-C-A

Variant summary

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

The NM_015052.5(HECW1):​c.-31-28864C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,160 control chromosomes in the GnomAD database, including 38,438 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 0.71 (38438 hom., cov: 33)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECW1	NM_015052.5	c.-31-28864C>A		intron_variant		ENST00000395891.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW1	ENST00000395891.7	c.-31-28864C>A		intron_variant		1	NM_015052.5	P2
HECW1	ENST00000453890.5	c.-31-28864C>A		intron_variant		2		A2
HECW1	ENST00000490954.2	n.310-96752C>A		intron_variant, non_coding_transcript_variant		4
HECW1	ENST00000492310.5	n.652-96752C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107757 AN: 152042 Hom.: 38396 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.709 AC: 107853 AN: 152160 Hom.: 38438 Cov.: 33 AF XY: 0.710 AC XY: 52848 AN XY: 74388

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.687

Alfa AF: 0.665 Hom.: 43451

Bravo AF: 0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1029482; hg19: chr7-43254610;