7-43337677-A-C

Variant names:

• chr7-43337677-A-C
• rs17172199
• NM_015052.5:c.460+16935A>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.460+16935A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,276 control chromosomes in the GnomAD database, including 277 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 0.053 (277 hom., cov: 32)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECW1	NM_015052.5	c.460+16935A>C		intron_variant	Intron 5 of 29	ENST00000395891.7	NP_055867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECW1	ENST00000395891.7	c.460+16935A>C		intron_variant	Intron 5 of 29	1	NM_015052.5	ENSP00000379228.1
HECW1	ENST00000453890.5	c.460+16935A>C		intron_variant	Intron 4 of 27	2		ENSP00000407774.1
HECW1	ENST00000492310.5	n.1084+16935A>C		intron_variant	Intron 3 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8010 AN: 152158 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0580

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

GnomAD4 genome AF: 0.0526 AC: 8006 AN: 152276 Hom.: 277 Cov.: 32 AF XY: 0.0530 AC XY: 3945 AN XY: 74452

African (AFR) AF: 0.0131 AC: 543 AN: 41580

American (AMR) AF: 0.0450 AC: 689 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5182

South Asian (SAS) AF: 0.101 AC: 488 AN: 4816

European-Finnish (FIN) AF: 0.0562 AC: 596 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5200 AN: 68004

Other (OTH) AF: 0.0573 AC: 121 AN: 2110

Alfa AF: 0.0368 Hom.: 62

Bravo AF: 0.0479

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.53
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17172199; hg19: chr7-43377276;