rs55704525

chr7-43528967-G-Achr7-43528967-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015052.5(HECW1):c.4020-12196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,188 control chromosomes in the GnomAD database, including 8 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 0.011 (8 hom., cov: 31)
• Consequence: HECW1 NM_015052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1603/152188) while in subpopulation NFE AF= 0.0171 (1161/67994). AF 95% confidence interval is 0.0163. There are 8 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1604 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECW1	NM_015052.5	c.4020-12196G>A		intron_variant		ENST00000395891.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECW1	ENST00000395891.7	c.4020-12196G>A		intron_variant		1	NM_015052.5	P2
HECW1	ENST00000429529.1	c.190+5821G>A		intron_variant		5
HECW1	ENST00000453890.5	c.3918-12196G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1604 AN: 152070 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0105 AC: 1603 AN: 152188 Hom.: 8 Cov.: 31 AF XY: 0.00903 AC XY: 672 AN XY: 74406

Gnomad4 AFR AF: 0.00304

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00334 Hom.: 0

Bravo AF: 0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.34

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: rs55704525; hg19: chr7-43568566;