chr7-75551049-A-G

Variant names:

• chr7-75551049-A-G
• rs6964720
• NM_005338.7:c.2296-2048T>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.2296-2048T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,188 control chromosomes in the GnomAD database, including 1,691 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 (1691 hom., cov: 32)
• Consequence: HIP1 NM_005338.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 14 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIP1	NM_005338.7	c.2296-2048T>C		intron_variant	Intron 22 of 30	ENST00000336926.11	NP_005329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIP1	ENST00000336926.11	c.2296-2048T>C		intron_variant	Intron 22 of 30	1	NM_005338.7	ENSP00000336747.6
HIP1	ENST00000616821.4	c.2209-2048T>C		intron_variant	Intron 22 of 30	1		ENSP00000484528.1
HIP1	ENST00000434438.6	c.2296-2048T>C		intron_variant	Intron 22 of 28	2		ENSP00000410300.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21094 AN: 152068 Hom.: 1691 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.139 AC: 21102 AN: 152188 Hom.: 1691 Cov.: 32 AF XY: 0.135 AC XY: 10054 AN XY: 74414

African (AFR) AF: 0.0719 AC: 2988 AN: 41546

American (AMR) AF: 0.122 AC: 1863 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5174

South Asian (SAS) AF: 0.172 AC: 830 AN: 4816

European-Finnish (FIN) AF: 0.0802 AC: 850 AN: 10604

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.180 AC: 12253 AN: 67992

Other (OTH) AF: 0.146 AC: 308 AN: 2112

Alfa AF: 0.169 Hom.: 3272

Bravo AF: 0.140

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.9
DANN	Benign	0.82
PhyloP100		0.24
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: rs6964720; hg19: chr7-75180344;