rs9322817

Positions:

• chr6-104784358-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.1478+59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,140,862 control chromosomes in the GnomAD database, including 79,259 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 0.42 (14207 hom., cov: 31)
  • Exomes 𝑓: 0.36 (65052 hom.)
• Consequence: HACE1 NM_020771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACE1	NM_020771.4	c.1478+59T>G		intron_variant		ENST00000262903.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACE1	ENST00000262903.9	c.1478+59T>G		intron_variant		1	NM_020771.4	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63375 AN: 151798 Hom.: 14188 Cov.: 31

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.358 AC: 354001 AN: 988946 Hom.: 65052 Cov.: 13 AF XY: 0.357 AC XY: 183111 AN XY: 513542

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.418 AC: 63449 AN: 151916 Hom.: 14207 Cov.: 31 AF XY: 0.412 AC XY: 30570 AN XY: 74242

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.389

Alfa AF: 0.367 Hom.: 11896

Bravo AF: 0.433

Asia WGS AF: 0.257 AC: 897 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.67

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: rs9322817; hg19: chr6-105232233; COSMIC: COSV53500225; COSMIC: COSV53500225;