dbSNP rs10515746: HAVCR2:c.-264-310T>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 ENST00000524219.2(HAVCR2):c.-293-2595T>G variant causes a intron 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
ENST00000524219.2 intron

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-related cancer predisposition
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

HAVCR2 links:

ENSG00000254246 (HGNC:):

ENSG00000254246 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000524219.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524219.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HAVCR2	ENST00000696899.1		c.-264-310T>G	intron	N/A	ENSP00000512960.1	Q8TDQ0-1
HAVCR2	ENST00000853244.1		c.-4-570T>G	intron	N/A	ENSP00000523303.1
HAVCR2	ENST00000524219.2	TSL:4	c.-293-2595T>G	intron	N/A	ENSP00000430328.2	E5RFR4

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over