5-157098909-A-AAGAG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_032782.5(HAVCR2):c.479-9_479-8insCTCT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,567,600 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (2 hom.)
• Consequence: HAVCR2 NM_032782.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.217

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 5-157098909-A-AAGAG is Benign according to our data. Variant chr5-157098909-A-AAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 3055791.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR2	NM_032782.5	c.479-9_479-8insCTCT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000307851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000307851.9	c.479-9_479-8insCTCT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032782.5	P2

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 711 AN: 149348 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00483

Gnomad ASJ AF: 0.00204

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00550

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00740

Gnomad OTH AF: 0.00443

GnomAD4 exome AF: 0.00607 AC: 8613 AN: 1418174 Hom.: 2 Cov.: 0 AF XY: 0.00588 AC XY: 4153 AN XY: 705886

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00329

Gnomad4 ASJ exome AF: 0.00163

Gnomad4 EAS exome AF: 0.000470

Gnomad4 SAS exome AF: 0.000515

Gnomad4 FIN exome AF: 0.00601

Gnomad4 NFE exome AF: 0.00714

Gnomad4 OTH exome AF: 0.00514

GnomAD4 genome AF: 0.00476 AC: 712 AN: 149426 Hom.: 1 Cov.: 32 AF XY: 0.00463 AC XY: 338 AN XY: 72924

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00476

Gnomad4 ASJ AF: 0.00204

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00550

Gnomad4 NFE AF: 0.00740

Gnomad4 OTH AF: 0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HAVCR2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs70984443; hg19: chr5-156525920;