dbSNP rs9322817: HACE1:c.1478+59T>G (chr6-104784358-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.946

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

spastic paraplegia-severe developmental delay-epilepsy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

HACE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HACE1	NM_020771.4 link	c.1478+59T>G		intron_variant	Intron 13 of 23	ENST00000262903.9	NP_065822.2	Q8IYU2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACE1	ENST00000262903.9 link	c.1478+59T>G		intron_variant	Intron 13 of 23	1	NM_020771.4	ENSP00000262903.4		Q8IYU2-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63375

AN:

151798

Hom.:

14188

Cov.:

show subpopulations

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.:

AF XY:

0.357

AC XY:

183111

AN XY:

513542

show subpopulations

African (AFR)

AF:

0.598

AC:

14468

AN:

24182

American (AMR)

AF:

0.371

AC:

16327

AN:

43956

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

6673

AN:

23250

East Asian (EAS)

AF:

0.254

AC:

9514

AN:

37518

South Asian (SAS)

AF:

0.333

AC:

25541

AN:

76686

European-Finnish (FIN)

AF:

0.321

AC:

17059

AN:

53162

Middle Eastern (MID)

AF:

0.408

AC:

1991

AN:

4876

European-Non Finnish (NFE)

AF:

0.362

AC:

245963

AN:

680376

Other (OTH)

AF:

0.366

AC:

16465

AN:

44940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12312

24623

36935

49246

61558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6052

12104

18156

24208

30260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.418

AC:

63449

AN:

151916

Hom.:

14207

Cov.:

AF XY:

0.412

AC XY:

30570

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.591

AC:

24488

AN:

41426

American (AMR)

AF:

0.382

AC:

5824

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

989

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1382

AN:

5160

South Asian (SAS)

AF:

0.307

AC:

1481

AN:

4820

European-Finnish (FIN)

AF:

0.326

AC:

3438

AN:

10532

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24551

AN:

67952

Other (OTH)

AF:

0.389

AC:

820

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1817

3634

5450

7267

9084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.391

Hom.:

22669

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

(source)

DANN

Benign

0.67

PhyloP100

0.95

PromoterAI

-0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over