Variant chr6-104734964-T-C details in Genebe, Genetics Data Aggregator

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

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]

HACE1 links:

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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
HACE1	NM_020771.4 link	c.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
HACE1	ENST00000262903.9 link	c.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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over