rs7213337

Positions:

• chr17-41723176-T-C
• chr17-41723176-T-G

Variant summary

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

The NM_177977.3(HAP1):​c.*1525A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,266 control chromosomes in the GnomAD database, including 55,207 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 0.85 (55168 hom., cov: 32)
  • Exomes 𝑓: 0.85 (39 hom.)
• Consequence: HAP1 NM_177977.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAP1	NM_177977.3	c.*1525A>G		3_prime_UTR_variant	11/11	ENST00000347901.9	NP_817084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAP1	ENST00000347901.9	c.*1525A>G		3_prime_UTR_variant	11/11	1	NM_177977.3	ENSP00000334002

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129396 AN: 152036 Hom.: 55124 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.848 AC: 95 AN: 112 Hom.: 39 Cov.: 0 AF XY: 0.833 AC XY: 70 AN XY: 84

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.851 AC: 129491 AN: 152154 Hom.: 55168 Cov.: 32 AF XY: 0.849 AC XY: 63165 AN XY: 74372

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.875

Alfa AF: 0.880 Hom.: 57186

Bravo AF: 0.849

Asia WGS AF: 0.896 AC: 3117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.75

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: rs7213337; hg19: chr17-39879428;