Variant 5-157098909-A-AAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000307851.9(HAVCR2):c.479-9_479-8insCT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,557,180 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 0 hom. )

Consequence

HAVCR2
ENST00000307851.9 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.217

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-157098909-A-AAG is Benign according to our data. Variant chr5-157098909-A-AAG is described in ClinVar as [Likely_benign]. Clinvar id is 3060989.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0046 (688/149414) while in subpopulation EAS AF= 0.0325 (167/5132). AF 95% confidence interval is 0.0285. There are 4 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR2	NM_032782.5 linkuse as main transcript	c.479-9_479-8insCT		splice_polypyrimidine_tract_variant, intron_variant		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.479-9_479-8insCT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032782.5	ENSP00000312002	P2	Q8TDQ0-1

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

689

AN:

149336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00800

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0105

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.000407

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000775

Gnomad OTH

AF:

0.00246

GnomAD4 exome

AF:

0.00333

AC:

4689

AN:

1407766

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

2377

AN XY:

700950

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00648

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.00923

Gnomad4 FIN exome

AF:

0.000805

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.00460

AC:

688

AN:

149414

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

364

AN XY:

72918

show subpopulations

Gnomad4 AFR

AF:

0.00802

Gnomad4 AMR

AF:

0.00254

Gnomad4 ASJ

AF:

0.0105

Gnomad4 EAS

AF:

0.0325

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.000407

Gnomad4 NFE

AF:

0.000775

Gnomad4 OTH

AF:

0.00244

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HAVCR2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 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

Splicing

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