7-75533848-G-A

Variant names:

• chr7-75533848-G-A
• rs1167827
• NM_005338.7:c.*4324C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005338.7(HIP1):​c.*4324C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 235,176 control chromosomes in the GnomAD database, including 25,500 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 0.38 (13949 hom., cov: 32)
  • Exomes 𝑓: 0.48 (11551 hom.)
• Consequence: HIP1 NM_005338.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 112 publications found

Genes affected

HIP1 (HGNC:4913): (huntingtin interacting protein 1) The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIP1	NM_005338.7	c.*4324C>T		3_prime_UTR_variant	Exon 31 of 31	ENST00000336926.11	NP_005329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIP1	ENST00000336926.11	c.*4324C>T		3_prime_UTR_variant	Exon 31 of 31	1	NM_005338.7	ENSP00000336747.6
HIP1	ENST00000434438.6	c.*4324C>T		downstream_gene_variant		2		ENSP00000410300.2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57891 AN: 152026 Hom.: 13934 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.485 AC: 40263 AN: 83030 Hom.: 11551 Cov.: 0 AF XY: 0.483 AC XY: 18538 AN XY: 38420

African (AFR) AF: 0.114 AC: 444 AN: 3910

American (AMR) AF: 0.569 AC: 1438 AN: 2528

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 2013 AN: 5166

East Asian (EAS) AF: 0.968 AC: 11261 AN: 11638

South Asian (SAS) AF: 0.497 AC: 358 AN: 720

European-Finnish (FIN) AF: 0.588 AC: 274 AN: 466

Middle Eastern (MID) AF: 0.331 AC: 168 AN: 508

European-Non Finnish (NFE) AF: 0.419 AC: 21468 AN: 51248

Other (OTH) AF: 0.415 AC: 2839 AN: 6846

GnomAD4 genome AF: 0.381 AC: 57923 AN: 152146 Hom.: 13949 Cov.: 32 AF XY: 0.394 AC XY: 29309 AN XY: 74364

African (AFR) AF: 0.116 AC: 4835 AN: 41548

American (AMR) AF: 0.542 AC: 8279 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3470

East Asian (EAS) AF: 0.938 AC: 4860 AN: 5182

South Asian (SAS) AF: 0.470 AC: 2269 AN: 4830

European-Finnish (FIN) AF: 0.565 AC: 5971 AN: 10564

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28946 AN: 67968

Other (OTH) AF: 0.402 AC: 848 AN: 2110

Alfa AF: 0.420 Hom.: 61355

Bravo AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
PhyloP100		0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1167827; hg19: chr7-75163169;