rs4336470

Positions:

• chr6-104732910-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020771.4(HACE1):​c.2514-2494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,982 control chromosomes in the GnomAD database, including 17,279 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 0.45 (17279 hom., cov: 33)
• Consequence: HACE1 NM_020771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

Genes affected

HACE1 (HGNC:21033): (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1) This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACE1	NM_020771.4	c.2514-2494G>A		intron_variant		ENST00000262903.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACE1	ENST00000262903.9	c.2514-2494G>A		intron_variant		1	NM_020771.4	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67584 AN: 151864 Hom.: 17241 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.445 AC: 67675 AN: 151982 Hom.: 17279 Cov.: 33 AF XY: 0.439 AC XY: 32580 AN XY: 74264

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.402

Alfa AF: 0.364 Hom.: 7026

Bravo AF: 0.466

Asia WGS AF: 0.262 AC: 912 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.94
DANN	Benign	0.52

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: rs4336470; hg19: chr6-105180785; COSMIC: COSV53500347; COSMIC: COSV53500347;