Genetic Variant HIP1:p.Ala173Ala (chr7-75582098-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005338.7(HIP1):c.519T>C(p.Ala173Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 1,613,564 control chromosomes in the GnomAD database, including 5,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 522 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4496 hom. )

Consequence

HIP1
NM_005338.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.80

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-75582098-A-G is Benign according to our data. Variant chr7-75582098-A-G is described in ClinVar as [Benign]. Clinvar id is 3059356.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIP1	NM_005338.7 link	c.519T>C	p.Ala173Ala	synonymous_variant	Exon 6 of 31	ENST00000336926.11	NP_005329.3	O00291-1B4DK46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HIP1	ENST00000336926.11 link	c.519T>C	p.Ala173Ala	synonymous_variant	Exon 6 of 31	1	NM_005338.7	ENSP00000336747.6	O00291-1
HIP1	ENST00000616821.4 link	c.432T>C	p.Ala144Ala	synonymous_variant	Exon 6 of 31	1		ENSP00000484528.1	O00291-4
HIP1	ENST00000434438.6 link	c.519T>C	p.Ala173Ala	synonymous_variant	Exon 6 of 29	2		ENSP00000410300.2	O00291-3
HIP1	ENST00000420909.1 link	c.432T>C	p.Ala144Ala	synonymous_variant	Exon 6 of 6	3		ENSP00000414280.1	C9JMG5

Frequencies

GnomAD3 genomes

AF:

0.0803

AC:

12204

AN:

152054

Hom.:

518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0633

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.0724

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0832

GnomAD3 exomes

AF:

0.0796

AC:

19944

AN:

250700

Hom.:

939

AF XY:

0.0834

AC XY:

11294

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0683

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0693

Gnomad NFE exome

AF:

0.0708

Gnomad OTH exome

AF:

0.0751

GnomAD4 exome

AF:

0.0740

AC:

108134

AN:

1461392

Hom.:

4496

Cov.:

AF XY:

0.0765

AC XY:

55626

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.0603

Gnomad4 ASJ exome

AF:

0.0535

Gnomad4 EAS exome

AF:

0.0530

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.0704

Gnomad4 NFE exome

AF:

0.0686

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.0803

AC:

12223

AN:

152172

Hom.:

522

Cov.:

AF XY:

0.0813

AC XY:

6050

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0633

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.0708

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.0818

Alfa

AF:

0.0733

Hom.:

692

Bravo

AF:

0.0777

Asia WGS

AF:

0.109

AC:

377

AN:

3478

EpiCase

AF:

0.0714

EpiControl

AF:

0.0708

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HIP1-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.72

CADD

Benign

2.6

DANN

Benign

0.62

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