rs17172185

Positions:

• chr7-43247240-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HECW1	NM_015052.5	c.27+3308T>C		intron_variant		ENST00000395891.7
LOC124901619	XR_007060295.1	n.117-1441A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW1	ENST00000395891.7	c.27+3308T>C		intron_variant		1	NM_015052.5	P2
	ENST00000457315.1	n.86+1943A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.0616

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0673 Hom.: 832

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

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: rs17172185; hg19: chr7-43286839;