dbSNP rs10515746: HAVCR2:n.-574T>G (chr5-157109557-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000696901.1(HAVCR2):n.-574T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,592 control chromosomes in the GnomAD database, including 48,984 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48798 hom., cov: 31)

Exomes 𝑓: 0.84 ( 186 hom. )

Consequence

HAVCR2
ENST00000696901.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240

Publications

72 publications found

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 Gene-Disease associations (from GenCC):

subcutaneous panniculitis-like T-cell lymphoma
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

HAVCR2 links:

ENSG00000254246 (HGNC:):

ENSG00000254246 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
HAVCR2	ENST00000696901.1 link	n.-574T>G	non_coding_transcript_exon_variant	Exon 1 of 5	ENSP00000512962.1	A0A8Q3SJ15
HAVCR2	ENST00000696901.1 link	n.-574T>G	5_prime_UTR_variant	Exon 1 of 5	ENSP00000512962.1	A0A8Q3SJ15
HAVCR2	ENST00000696899.1 link	c.-264-310T>G	intron_variant	Intron 1 of 7	ENSP00000512960.1	Q8TDQ0-1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121180

AN:

151956

Hom.:

48762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.895

Gnomad AMR

AF:

0.862

Gnomad ASJ

AF:

0.880

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.940

Gnomad FIN

AF:

0.853

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.806

GnomAD4 exome

AF:

0.840

AC:

435

AN:

518

Hom.:

186

Cov.:

AF XY:

0.844

AC XY:

211

AN XY:

250

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.902

AC:

101

AN:

112

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.875

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.812

AC:

281

AN:

346

Other (OTH)

AF:

0.900

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.797

AC:

121269

AN:

152074

Hom.:

48798

Cov.:

AF XY:

0.805

AC XY:

59854

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.692

AC:

28692

AN:

41452

American (AMR)

AF:

0.862

AC:

13164

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

3054

AN:

3470

East Asian (EAS)

AF:

0.987

AC:

5104

AN:

5170

South Asian (SAS)

AF:

0.940

AC:

4521

AN:

4810

European-Finnish (FIN)

AF:

0.853

AC:

9022

AN:

10580

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.808

AC:

54959

AN:

67998

Other (OTH)

AF:

0.808

AC:

1709

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1237

2475

3712

4950

6187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.732

Hom.:

2507

Bravo

AF:

0.793

Asia WGS

AF:

0.941

AC:

3274

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.79

(source)

DANN

Benign

0.54

PhyloP100

-0.24

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over