Variant 5-157104854-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032782.5(HAVCR2):c.395-105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 715,932 control chromosomes in the GnomAD database, including 250,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.83 ( 53065 hom., cov: 31)

Exomes 𝑓: 0.83 ( 197087 hom. )

Consequence

HAVCR2
NM_032782.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00100

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:

(HGNC:):

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=-0.87).

BP6

Variant 5-157104854-A-G is Benign according to our data. Variant chr5-157104854-A-G is described in ClinVar as [Benign]. Clinvar id is 2688155.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR2	NM_032782.5 linkuse as main transcript	c.395-105T>C		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.395-105T>C		intron_variant		1	NM_032782.5	ENSP00000312002	P2	Q8TDQ0-1
	ENST00000517708.1 linkuse as main transcript	n.67A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126829

AN:

152052

Hom.:

53028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.853

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.838

GnomAD4 exome

AF:

0.833

AC:

469886

AN:

563762

Hom.:

197087

Cov.:

AF XY:

0.839

AC XY:

248931

AN XY:

296752

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.908

Gnomad4 ASJ exome

AF:

0.878

Gnomad4 EAS exome

AF:

0.981

Gnomad4 SAS exome

AF:

0.946

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.798

Gnomad4 OTH exome

AF:

0.837

GnomAD4 genome

AF:

0.834

AC:

126924

AN:

152170

Hom.:

53065

Cov.:

AF XY:

0.840

AC XY:

62506

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.801

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.952

Gnomad4 FIN

AF:

0.853

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.840

Alfa

AF:

0.811

Hom.:

5495

Bravo

AF:

0.836

Asia WGS

AF:

0.955

AC:

3321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

DANN

Benign

0.47

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