Genetic Variant HAVCR2:c.*931C>G (chr5-157086171-G-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.*931C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,248 control chromosomes in the GnomAD database, including 53,401 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 0.84 ( 53379 hom., cov: 32)

Exomes 𝑓: 0.84 ( 22 hom. )

Consequence

HAVCR2
NM_032782.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

12 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:

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=-0.72).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032782.5. 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
	HAVCR2	NM_032782.5	MANE Select	c.*931C>G		3_prime_UTR	Exon 7 of 7	NP_116171.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.*931C>G	3_prime_UTR	Exon 7 of 7	ENSP00000312002.4	Q8TDQ0-1
HAVCR2	ENST00000696899.1		c.*931C>G	3_prime_UTR	Exon 8 of 8	ENSP00000512960.1	Q8TDQ0-1
HAVCR2	ENST00000696902.1		c.*931C>G	3_prime_UTR	Exon 7 of 7	ENSP00000512963.1	A0A8Q3SJ74

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

127139

AN:

152072

Hom.:

53329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.840

GnomAD4 exome

AF:

0.845

AC:

AN:

Hom.:

Cov.:

AF XY:

0.850

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.854

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.836

AC:

127247

AN:

152190

Hom.:

53379

Cov.:

AF XY:

0.844

AC XY:

62825

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.796

AC:

33029

AN:

41504

American (AMR)

AF:

0.893

AC:

13647

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.888

AC:

3082

AN:

3472

East Asian (EAS)

AF:

0.987

AC:

5113

AN:

5182

South Asian (SAS)

AF:

0.953

AC:

4595

AN:

4824

European-Finnish (FIN)

AF:

0.859

AC:

9090

AN:

10588

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55851

AN:

68018

Other (OTH)

AF:

0.842

AC:

1778

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1074

2148

3222

4296

5370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.750

Hom.:

1568

Bravo

AF:

0.836

Asia WGS

AF:

0.960

AC:

3338

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.6

(source)

DANN

Benign

0.74

PhyloP100

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over