Genetic Variant HAP1:c.*1839G>A (chr17-41722862-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_177977.3(HAP1):c.*1839G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,542 control chromosomes in the GnomAD database, including 45,807 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 0.76 ( 45674 hom., cov: 27)

Exomes 𝑓: 0.85 ( 133 hom. )

Consequence

HAP1
NM_177977.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.77

Publications

5 publications found

Variant links:

Genes affected

HAP1 (HGNC:4812): (huntingtin associated protein 1) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar autoantigen protein 1), and with a hepatocyte growth factor-regulated tyrosine kinase substrate. The interactions with cytoskeletal proteins and a kinase substrate suggest a role for this protein in vesicular trafficking or organelle transport. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

HAP1 links:

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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=-0.98).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAP1	NM_177977.3 link	c.*1839G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000347901.9	NP_817084.2	P54257-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAP1	ENST00000347901.9 link	c.*1839G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_177977.3	ENSP00000334002.4		P54257-2

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

115350

AN:

151052

Hom.:

45664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.812

GnomAD4 exome

AF:

0.854

AC:

316

AN:

370

Hom.:

133

Cov.:

AF XY:

0.863

AC XY:

195

AN XY:

226

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.779

AC:

AN:

Middle Eastern (MID)

AF:

0.889

AC:

AN:

European-Non Finnish (NFE)

AF:

0.901

AC:

200

AN:

222

Other (OTH)

AF:

0.810

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.763

AC:

115399

AN:

151172

Hom.:

45674

Cov.:

AF XY:

0.766

AC XY:

56482

AN XY:

73780

show subpopulations

African (AFR)

AF:

0.530

AC:

21750

AN:

41070

American (AMR)

AF:

0.796

AC:

12110

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

2955

AN:

3470

East Asian (EAS)

AF:

0.884

AC:

4458

AN:

5042

South Asian (SAS)

AF:

0.906

AC:

4320

AN:

4768

European-Finnish (FIN)

AF:

0.788

AC:

8228

AN:

10444

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58771

AN:

67856

Other (OTH)

AF:

0.813

AC:

1718

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1126

2252

3377

4503

5629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.789

Hom.:

11522

Bravo

AF:

0.749

Asia WGS

AF:

0.863

AC:

2997

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.070

(source)

DANN

Benign

0.20

PhyloP100

-2.8

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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chr17-41722862-C-T

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