7-75606231-T-G

Variant names:

• chr7-75606231-T-G
• rs17149227
• NM_005338.7:c.121-6984A>C

Variant summary

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

The NM_005338.7(HIP1):​c.121-6984A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,124 control chromosomes in the GnomAD database, including 2,319 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 0.14 (2319 hom., cov: 31)
• Consequence: HIP1 NM_005338.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005338.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	NM_005338.7	MANE Select	c.121-6984A>C		intron	N/A	NP_005329.3
	HIP1	NM_001382445.1		c.33+5435A>C		intron	N/A	NP_001369374.1
	HIP1	NM_001382444.1		c.19-6984A>C		intron	N/A	NP_001369373.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	ENST00000336926.11	TSL:1 MANE Select	c.121-6984A>C		intron	N/A	ENSP00000336747.6
	HIP1	ENST00000616821.4	TSL:1	c.33+5435A>C		intron	N/A	ENSP00000484528.1
	HIP1	ENST00000434438.6	TSL:2	c.121-6984A>C		intron	N/A	ENSP00000410300.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20737 AN: 152006 Hom.: 2309 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20777 AN: 152124 Hom.: 2319 Cov.: 31 AF XY: 0.140 AC XY: 10380 AN XY: 74384

African (AFR) AF: 0.263 AC: 10907 AN: 41500

American (AMR) AF: 0.217 AC: 3308 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5170

South Asian (SAS) AF: 0.199 AC: 959 AN: 4820

European-Finnish (FIN) AF: 0.0659 AC: 698 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3066 AN: 67996

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.0746 Hom.: 1070

Bravo AF: 0.153

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17149227; hg19: chr7-75235549;