6-104743939-C-T

Position:

• chr6-104743939-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.2513+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,866 control chromosomes in the GnomAD database, including 17,858 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 (17858 hom., cov: 32)
• Consequence: HACE1 NM_020771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACE1	NM_020771.4	c.2513+221G>A		intron_variant		ENST00000262903.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACE1	ENST00000262903.9	c.2513+221G>A		intron_variant		1	NM_020771.4	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69004 AN: 151748 Hom.: 17820 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.455 AC: 69095 AN: 151866 Hom.: 17858 Cov.: 32 AF XY: 0.448 AC XY: 33254 AN XY: 74214

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.411

Alfa AF: 0.362 Hom.: 11309

Bravo AF: 0.474

Asia WGS AF: 0.260 AC: 902 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.032
DANN	Benign	0.19

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: rs6942231; hg19: chr6-105191814; COSMIC: COSV53500417;