Variant 7-75542951-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005338.7(HIP1):c.2790C>T(p.Pro930=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,358 control chromosomes in the GnomAD database, including 20,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1476 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18959 hom. )

Consequence

HIP1
NM_005338.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.56

Variant links:

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]

HIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 7-75542951-G-A is Benign according to our data. Variant chr7-75542951-G-A is described in ClinVar as [Benign]. Clinvar id is 3055297.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIP1	NM_005338.7 linkuse as main transcript	c.2790C>T	p.Pro930=	synonymous_variant	28/31	ENST00000336926.11	NP_005329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIP1	ENST00000336926.11 linkuse as main transcript	c.2790C>T	p.Pro930=	synonymous_variant	28/31	1	NM_005338.7	ENSP00000336747	P1	O00291-1
HIP1	ENST00000616821.4 linkuse as main transcript	c.2703C>T	p.Pro901=	synonymous_variant	28/31	1		ENSP00000484528		O00291-4
HIP1	ENST00000434438.6 linkuse as main transcript	c.2637C>T	p.Pro879=	synonymous_variant	26/29	2		ENSP00000410300		O00291-3

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19347

AN:

151962

Hom.:

1472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0650

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0994

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0891

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.131

AC:

32904

AN:

251062

Hom.:

2721

AF XY:

0.134

AC XY:

18208

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.0618

Gnomad AMR exome

AF:

0.0625

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.0972

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.155

AC:

226797

AN:

1461278

Hom.:

18959

Cov.:

AF XY:

0.155

AC XY:

112450

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.0671

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.0977

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.127

AC:

19361

AN:

152080

Hom.:

1476

Cov.:

AF XY:

0.128

AC XY:

9516

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0650

Gnomad4 AMR

AF:

0.0993

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0904

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.155

Hom.:

1987

Bravo

AF:

0.117

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HIP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.6

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over