ENST00000481065.5:c.-434T>C

Variant names:

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

Variant summary

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

The ENST00000481065.5(TIGIT):​c.-434T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 181,726 control chromosomes in the GnomAD database, including 23,494 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 0.49 (21159 hom., cov: 32)
  • Exomes 𝑓: 0.37 (2335 hom.)
• Consequence: TIGIT ENST00000481065.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

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>C		5_prime_UTR_variant	Exon 2 of 5	2		ENSP00000420552.1
TIGIT	ENST00000486257.5	c.-62-573T>C		intron_variant	Intron 1 of 4	5		ENSP00000419085.1
TIGIT	ENST00000461158.5	c.-2-2118T>C		intron_variant	Intron 1 of 3	4		ENSP00000418917.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74517 AN: 151980 Hom.: 21113 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.366 AC: 10837 AN: 29628 Hom.: 2335 Cov.: 0 AF XY: 0.369 AC XY: 5870 AN XY: 15898

African (AFR) AF: 0.750 AC: 441 AN: 588

American (AMR) AF: 0.313 AC: 979 AN: 3132

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 271 AN: 590

East Asian (EAS) AF: 0.0861 AC: 179 AN: 2078

South Asian (SAS) AF: 0.416 AC: 1581 AN: 3802

European-Finnish (FIN) AF: 0.307 AC: 296 AN: 964

Middle Eastern (MID) AF: 0.609 AC: 39 AN: 64

European-Non Finnish (NFE) AF: 0.383 AC: 6562 AN: 17142

Other (OTH) AF: 0.386 AC: 489 AN: 1268

GnomAD4 genome AF: 0.491 AC: 74614 AN: 152098 Hom.: 21159 Cov.: 32 AF XY: 0.480 AC XY: 35676 AN XY: 74322

African (AFR) AF: 0.780 AC: 32354 AN: 41504

American (AMR) AF: 0.352 AC: 5384 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3472

East Asian (EAS) AF: 0.0961 AC: 497 AN: 5174

South Asian (SAS) AF: 0.448 AC: 2153 AN: 4810

European-Finnish (FIN) AF: 0.297 AC: 3139 AN: 10572

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27924 AN: 67962

Other (OTH) AF: 0.478 AC: 1010 AN: 2112

Alfa AF: 0.439 Hom.: 47336

Bravo AF: 0.504

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.57
PhyloP100		-1.6
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: rs1039524; hg19: chr3-114012274;