chr6-104734964-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020771.4(HACE1):​c.2514-4548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,860 control chromosomes in the GnomAD database, including 25,193 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 0.56 ( 25193 hom., cov: 32)

Consequence

HACE1
NM_020771.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.177
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HACE1NM_020771.4 linkc.2514-4548A>G intron_variant ENST00000262903.9 NP_065822.2 Q8IYU2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HACE1ENST00000262903.9 linkc.2514-4548A>G intron_variant 1 NM_020771.4 ENSP00000262903.4 Q8IYU2-1

Frequencies

GnomAD3 genomes
AF:
0.556
AC:
84387
AN:
151744
Hom.:
25156
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.792
Gnomad AMI
AF:
0.443
Gnomad AMR
AF:
0.542
Gnomad ASJ
AF:
0.390
Gnomad EAS
AF:
0.423
Gnomad SAS
AF:
0.465
Gnomad FIN
AF:
0.475
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.456
Gnomad OTH
AF:
0.514
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.556
AC:
84469
AN:
151860
Hom.:
25193
Cov.:
32
AF XY:
0.555
AC XY:
41189
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.792
Gnomad4 AMR
AF:
0.541
Gnomad4 ASJ
AF:
0.390
Gnomad4 EAS
AF:
0.423
Gnomad4 SAS
AF:
0.464
Gnomad4 FIN
AF:
0.475
Gnomad4 NFE
AF:
0.456
Gnomad4 OTH
AF:
0.509
Alfa
AF:
0.481
Hom.:
3594
Bravo
AF:
0.575
Asia WGS
AF:
0.408
AC:
1416
AN:
3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
8.4
DANN
Benign
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7741733; hg19: chr6-105182839; COSMIC: COSV53506898; COSMIC: COSV53506898; API