chr7-43528967-G-A

Variant names:

• chr7-43528967-G-A
• rs55704525
• NM_015052.5:c.4020-12196G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1603 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015052.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECW1	NM_015052.5	MANE Select	c.4020-12196G>A		intron	N/A	NP_055867.3	Q76N89-1
	HECW1	NM_001287059.2		c.3918-12196G>A		intron	N/A	NP_001273988.1	Q76N89-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECW1	ENST00000395891.7	TSL:1 MANE Select	c.4020-12196G>A		intron	N/A	ENSP00000379228.1	Q76N89-1
	HECW1	ENST00000857209.1		c.4020-12196G>A		intron	N/A	ENSP00000527268.1
	HECW1	ENST00000453890.5	TSL:2	c.3918-12196G>A		intron	N/A	ENSP00000407774.1	Q76N89-2

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

African (AFR) AF: 0.00304 AC: 126 AN: 41512

American (AMR) AF: 0.00981 AC: 150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4822

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1161 AN: 67994

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.0141 Hom.: 21

Bravo AF: 0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism

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: rs55704525; hg19: chr7-43568566;