dbSNP rs13170556: HAVCR2:c.523-118A>G (chr5-157095577-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032782.5(HAVCR2):c.523-118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,066,734 control chromosomes in the GnomAD database, including 12,495 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 0.13 ( 1405 hom., cov: 31)

Exomes 𝑓: 0.15 ( 11090 hom. )

Consequence

HAVCR2
NM_032782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.853

Publications

7 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:

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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR2	NM_032782.5 link	c.523-118A>G		intron_variant	Intron 4 of 6	ENST00000307851.9	NP_116171.3	Q8TDQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000307851.9 link	c.523-118A>G		intron_variant	Intron 4 of 6	1	NM_032782.5	ENSP00000312002.4		Q8TDQ0-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19946

AN:

152006

Hom.:

1405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0855

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.152

AC:

139127

AN:

914610

Hom.:

11090

AF XY:

0.155

AC XY:

72269

AN XY:

465458

show subpopulations

African (AFR)

AF:

0.0861

AC:

1896

AN:

22026

American (AMR)

AF:

0.134

AC:

4233

AN:

31500

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2046

AN:

18826

East Asian (EAS)

AF:

0.199

AC:

6893

AN:

34596

South Asian (SAS)

AF:

0.223

AC:

13970

AN:

62644

European-Finnish (FIN)

AF:

0.149

AC:

5625

AN:

37724

Middle Eastern (MID)

AF:

0.165

AC:

601

AN:

3638

European-Non Finnish (NFE)

AF:

0.148

AC:

97708

AN:

661682

Other (OTH)

AF:

0.147

AC:

6155

AN:

41974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5811

11621

17432

23242

29053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2910

5820

8730

11640

14550

<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:

0.131

AC:

19956

AN:

152124

Hom.:

1405

Cov.:

AF XY:

0.133

AC XY:

9912

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0856

AC:

3555

AN:

41512

American (AMR)

AF:

0.130

AC:

1983

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.173

AC:

896

AN:

5180

South Asian (SAS)

AF:

0.222

AC:

1068

AN:

4820

European-Finnish (FIN)

AF:

0.145

AC:

1533

AN:

10574

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10122

AN:

67986

Other (OTH)

AF:

0.127

AC:

267

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

876

1752

2628

3504

4380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.141

Hom.:

2625

Bravo

AF:

0.125

Asia WGS

AF:

0.174

AC:

607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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