5-157104854-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032782.5(HAVCR2):c.395-105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 715,932 control chromosomes in the GnomAD database, including 250,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (53065 hom., cov: 31)
  • Exomes 𝑓: 0.83 (197087 hom.)
• Consequence: HAVCR2 NM_032782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-157104854-A-G is Benign according to our data. Variant chr5-157104854-A-G is described in ClinVar as [Benign]. Clinvar id is 2688155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR2	NM_032782.5	c.395-105T>C		intron_variant		ENST00000307851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000307851.9	c.395-105T>C		intron_variant		1	NM_032782.5	P2
	ENST00000517708.1	n.67A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126829 AN: 152052 Hom.: 53028 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.838

GnomAD4 exome AF: 0.833 AC: 469886 AN: 563762 Hom.: 197087 Cov.: 8 AF XY: 0.839 AC XY: 248931 AN XY: 296752

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.834 AC: 126924 AN: 152170 Hom.: 53065 Cov.: 31 AF XY: 0.840 AC XY: 62506 AN XY: 74386

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.840

Alfa AF: 0.811 Hom.: 5495

Bravo AF: 0.836

Asia WGS AF: 0.955 AC: 3321 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1036200; hg19: chr5-156531865; COSMIC: COSV104410902; COSMIC: COSV104410902;