Variant 5-157087178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032782.5(HAVCR2):c.830C>T(p.Pro277Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0111 in 1,613,956 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 33)

Exomes 𝑓: 0.011 ( 122 hom. )

Consequence

HAVCR2
NM_032782.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

HAVCR2 (HGNC:18437): (hepatitis A virus cellular receptor 2) The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

HAVCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040649474).

BP6

Variant 5-157087178-G-A is Benign according to our data. Variant chr5-157087178-G-A is described in ClinVar as [Benign]. Clinvar id is 782945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR2	NM_032782.5 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	7/7	ENST00000307851.9	NP_116171.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000307851.9 linkuse as main transcript	c.830C>T	p.Pro277Leu	missense_variant	7/7	1	NM_032782.5	ENSP00000312002	P2	Q8TDQ0-1

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1170

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00808

AC:

2029

AN:

251216

Hom.:

AF XY:

0.00840

AC XY:

1141

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.00904

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00425

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0115

AC:

16759

AN:

1461684

Hom.:

122

Cov.:

AF XY:

0.0114

AC XY:

8268

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00236

Gnomad4 AMR exome

AF:

0.00640

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00451

Gnomad4 FIN exome

AF:

0.00328

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.00980

GnomAD4 genome

AF:

0.00770

AC:

1172

AN:

152272

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

528

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00890

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00852

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0151

AC:

130

ExAC

AF:

0.00845

AC:

1026

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0110

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	HAVCR2: BP4, BS1, BS2 -

HAVCR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 25, 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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.092

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.74

P;.

Vest4

0.27

MVP

0.33

MPC

0.13

ClinPred

0.025

GERP RS

4.5

Varity_R

0.058

gMVP

0.61

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