rs4704846

Variant names:

• chr5-157086333-G-A
• rs4704846
• NM_032782.5:c.*769C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-157086333-G-A
• chr5-157086333-G-C
• chr5-157086333-G-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.*769C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,202 control chromosomes in the GnomAD database, including 48,581 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 0.79 (48581 hom., cov: 33)
  • Exomes 𝑓: 0.81 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: HAVCR2 NM_032782.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 14 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=-0.91).
• 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.*769C>T		3_prime_UTR	Exon 7 of 7	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.*769C>T		3_prime_UTR	Exon 7 of 7	ENSP00000312002.4	Q8TDQ0-1
	HAVCR2	ENST00000696899.1		c.*769C>T		3_prime_UTR	Exon 8 of 8	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000696902.1		c.*769C>T		3_prime_UTR	Exon 7 of 7	ENSP00000512963.1	A0A8Q3SJ74

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120867 AN: 152084 Hom.: 48548 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.806

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.813 AC: 26 AN: 32 Hom.: 11 Cov.: 0 AF XY: 0.818 AC XY: 18 AN XY: 22

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.821 AC: 23 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.795 AC: 120952 AN: 152202 Hom.: 48581 Cov.: 33 AF XY: 0.803 AC XY: 59776 AN XY: 74416

African (AFR) AF: 0.672 AC: 27904 AN: 41516

American (AMR) AF: 0.864 AC: 13207 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5113 AN: 5182

South Asian (SAS) AF: 0.951 AC: 4592 AN: 4830

European-Finnish (FIN) AF: 0.853 AC: 9035 AN: 10590

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55280 AN: 68010

Other (OTH) AF: 0.807 AC: 1704 AN: 2112

Alfa AF: 0.802 Hom.: 30030

Bravo AF: 0.791

Asia WGS AF: 0.945 AC: 3286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.35
PhyloP100		-0.26
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: rs4704846; hg19: chr5-156513344;