17-41722862-C-T

Variant names:

• chr17-41722862-C-T
• rs12951847
• NM_177977.3:c.*1839G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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]

ACMG classification

Verdict is Benign. Variant got -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	c.*1839G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000347901.9	NP_817084.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115350 AN: 151052 Hom.: 45664 Cov.: 27

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.: 0 AF XY: 0.863 AC XY: 195 AN XY: 226

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.779

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.810

GnomAD4 genome AF: 0.763 AC: 115399 AN: 151172 Hom.: 45674 Cov.: 27 AF XY: 0.766 AC XY: 56482 AN XY: 73780

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.813

Alfa AF: 0.795 Hom.: 11410

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
DANN	Benign	0.20

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: rs12951847; hg19: chr17-39879114; COSMIC: COSV57881015; COSMIC: COSV57881015;