chr5-157110499-C-A

Variant names:

• chr5-157110499-C-A
• rs10053538
• ENST00000696899.1:c.-264-1252G>T

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-293-3537G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 151,832 control chromosomes in the GnomAD database, including 433 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 0.061 (433 hom., cov: 32)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 47 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
• HAVCR2-related cancer predisposition

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000254246 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000696899.1		c.-264-1252G>T		intron	N/A	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.-4-1512G>T		intron	N/A	ENSP00000523303.1
	HAVCR2	ENST00000524219.2	TSL:4	c.-293-3537G>T		intron	N/A	ENSP00000430328.2	E5RFR4

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9267 AN: 151714 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0612 AC: 9297 AN: 151832 Hom.: 433 Cov.: 32 AF XY: 0.0643 AC XY: 4774 AN XY: 74190

African (AFR) AF: 0.0375 AC: 1553 AN: 41414

American (AMR) AF: 0.144 AC: 2192 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3464

East Asian (EAS) AF: 0.0564 AC: 289 AN: 5124

South Asian (SAS) AF: 0.113 AC: 543 AN: 4800

European-Finnish (FIN) AF: 0.0934 AC: 984 AN: 10530

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3501 AN: 67948

Other (OTH) AF: 0.0441 AC: 92 AN: 2088

Alfa AF: 0.0231 Hom.: 7

Bravo AF: 0.0659

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		0.21

Splicing

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.

Other links and lift over

dbSNP: rs10053538;

hg19: chr5-156537510;