NM_015052.5:c.27+3308T>C

Variant names:

• chr7-43247240-T-C
• rs17172185
• NM_015052.5:c.27+3308T>C

Variant summary

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

The NM_015052.5(HECW1):​c.27+3308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,194 control chromosomes in the GnomAD database, including 2,673 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 0.14 (2673 hom., cov: 32)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 8 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]

ENSG00000228680 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECW1	NM_015052.5	c.27+3308T>C		intron_variant	Intron 3 of 29	ENST00000395891.7	NP_055867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECW1	ENST00000395891.7	c.27+3308T>C		intron_variant	Intron 3 of 29	1	NM_015052.5	ENSP00000379228.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20692 AN: 152076 Hom.: 2659 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.136 AC: 20747 AN: 152194 Hom.: 2673 Cov.: 32 AF XY: 0.133 AC XY: 9922 AN XY: 74420

African (AFR) AF: 0.335 AC: 13888 AN: 41486

American (AMR) AF: 0.0707 AC: 1082 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5170

South Asian (SAS) AF: 0.0616 AC: 297 AN: 4820

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3459 AN: 68022

Other (OTH) AF: 0.125 AC: 263 AN: 2108

Alfa AF: 0.0783 Hom.: 1682

Bravo AF: 0.153

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.36
PhyloP100		0.13
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: rs17172185; hg19: chr7-43286839;