Variant chr7-75539357-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005338.7(HIP1):c.3027C>T(p.Tyr1009=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,614,090 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00088 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 31 hom. )

Consequence

HIP1
NM_005338.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.334

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-75539357-G-A is Benign according to our data. Variant chr7-75539357-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041842.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.334 with no splicing effect.

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIP1	NM_005338.7 linkuse as main transcript	c.3027C>T	p.Tyr1009=	synonymous_variant	30/31	ENST00000336926.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIP1	ENST00000336926.11 linkuse as main transcript	c.3027C>T	p.Tyr1009=	synonymous_variant	30/31	1	NM_005338.7	P1	O00291-1
HIP1	ENST00000616821.4 linkuse as main transcript	c.2940C>T	p.Tyr980=	synonymous_variant	30/31	1			O00291-4
HIP1	ENST00000434438.6 linkuse as main transcript	c.2874C>T	p.Tyr958=	synonymous_variant	28/29	2			O00291-3

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00223

AC:

561

AN:

251488

Hom.:

AF XY:

0.00283

AC XY:

384

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00119

AC:

1737

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1188

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00627

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000188

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152266

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000801

Hom.:

Bravo

AF:

0.000389

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HIP1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 25, 2019

This variant is classified as likely 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

-0.48

CADD

Benign

1.5

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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