rs1039524

Positions:

• chr3-114293427-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGIT	ENST00000481065.5	c.-434T>C		5_prime_UTR_variant	2/5	2		ENSP00000420552
TIGIT	ENST00000461158.5	c.-2-2118T>C		intron_variant		4		ENSP00000418917
TIGIT	ENST00000486257.5	c.-62-573T>C		intron_variant		5		ENSP00000419085	P1

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.0861

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.386

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.478

Alfa AF: 0.429 Hom.: 19566

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

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: rs1039524; hg19: chr3-114012274;