chr5-157089149-G-A

Variant names:

• chr5-157089149-G-A
• rs9313441
• NM_032782.5:c.677-172C>T

Variant summary

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

The NM_032782.5(HAVCR2):​c.677-172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,264 control chromosomes in the GnomAD database, including 426 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 (426 hom., cov: 32)
• Consequence: HAVCR2 NM_032782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 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.677-172C>T		intron	N/A	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.677-172C>T		intron	N/A	ENSP00000312002.4	Q8TDQ0-1
	HAVCR2	ENST00000696899.1		c.677-172C>T		intron	N/A	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.677-172C>T		intron	N/A	ENSP00000523303.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9257 AN: 152146 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0610 AC: 9288 AN: 152264 Hom.: 426 Cov.: 32 AF XY: 0.0641 AC XY: 4774 AN XY: 74446

African (AFR) AF: 0.0368 AC: 1529 AN: 41550

American (AMR) AF: 0.142 AC: 2179 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.0565 AC: 293 AN: 5184

South Asian (SAS) AF: 0.115 AC: 554 AN: 4822

European-Finnish (FIN) AF: 0.0931 AC: 987 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0516 AC: 3509 AN: 68028

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0547 Hom.: 44

Bravo AF: 0.0655

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9313441; hg19: chr5-156516160;