6-104840250-A-C

Position:

• chr6-104840250-A-C

Variant summary

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

The NM_020771.4(HACE1):​c.402+2973T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,248 control chromosomes in the GnomAD database, including 972 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 0.11 (972 hom., cov: 32)
• Consequence: HACE1 NM_020771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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]

ENSG00000227535 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HACE1	NM_020771.4	c.402+2973T>G		intron_variant		ENST00000262903.9	NP_065822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HACE1	ENST00000262903.9	c.402+2973T>G		intron_variant		1	NM_020771.4	ENSP00000262903.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16825 AN: 152130 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.110 AC: 16814 AN: 152248 Hom.: 972 Cov.: 32 AF XY: 0.116 AC XY: 8606 AN XY: 74424

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.104

Alfa AF: 0.112 Hom.: 1033

Bravo AF: 0.109

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.77

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: rs6927608; hg19: chr6-105288125; COSMIC: COSV53507308; COSMIC: COSV53507308;