chr3-114293427-T-A

Variant names:

• chr3-114293427-T-A
• rs1039524
• ENST00000481065.5:c.-434T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000481065.5(TIGIT):​c.-434T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIGIT ENST00000481065.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

Genes affected

TIGIT (HGNC:26838): (T cell immunoreceptor with Ig and ITIM domains) This gene encodes a member of the PVR (poliovirus receptor) family of immunoglobin proteins. The product of this gene is expressed on several classes of T cells including follicular B helper T cells (TFH). The protein has been shown to bind PVR with high affinity; this binding is thought to assist interactions between TFH and dendritic cells to regulate T cell dependent B cell responses.[provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGIT	ENST00000481065.5	c.-434T>A		5_prime_UTR_variant	Exon 2 of 5	2		ENSP00000420552.1
TIGIT	ENST00000486257.5	c.-62-573T>A		intron_variant	Intron 1 of 4	5		ENSP00000419085.1
TIGIT	ENST00000461158.5	c.-2-2118T>A		intron_variant	Intron 1 of 3	4		ENSP00000418917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 29736 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 15970

African (AFR) AF: 0.00 AC: 0 AN: 588

American (AMR) AF: 0.00 AC: 0 AN: 3158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 590

East Asian (EAS) AF: 0.00 AC: 0 AN: 2084

South Asian (SAS) AF: 0.00 AC: 0 AN: 3822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 64

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17186

Other (OTH) AF: 0.00 AC: 0 AN: 1272

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.61
PhyloP100		-1.6

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: rs1039524; hg19: chr3-114012274;