5-157127653-G-A

Variant names:

• chr5-157127653-G-A
• rs418899
• ENST00000524219.2:c.-294+15167C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524219.2(HAVCR2):​c.-294+15167C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 150,984 control chromosomes in the GnomAD database, including 10,642 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 0.36 (10642 hom., cov: 32)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000524219.2	TSL:4	c.-294+15167C>T		intron	N/A	ENSP00000430328.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53607 AN: 150876 Hom.: 10607 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 53683 AN: 150984 Hom.: 10642 Cov.: 32 AF XY: 0.350 AC XY: 25788 AN XY: 73610

African (AFR) AF: 0.551 AC: 22690 AN: 41174

American (AMR) AF: 0.274 AC: 4144 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3462

East Asian (EAS) AF: 0.189 AC: 968 AN: 5110

South Asian (SAS) AF: 0.259 AC: 1240 AN: 4792

European-Finnish (FIN) AF: 0.264 AC: 2677 AN: 10158

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20160 AN: 67836

Other (OTH) AF: 0.333 AC: 699 AN: 2100

Alfa AF: 0.318 Hom.: 1654

Bravo AF: 0.361

Asia WGS AF: 0.235 AC: 819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.32
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs418899; hg19: chr5-156554664;