14-22533736-G-T

Variant names:

• chr14-22533736-G-T
• rs1154155

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.855 in 152,172 control chromosomes in the GnomAD database, including 56,262 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 0.86 (56262 hom., cov: 31)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

Genes affected

TRA (HGNC:12027):

TRAJ10 (HGNC:12038): (T cell receptor alpha joining 10) T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. If not, the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor alpha and delta loci. Both the alpha and delta loci include V (variable), J (joining), and C (constant) segments and the delta locus also includes diversity (D) segments. The delta locus is situated within the alpha locus, between the alpha V and J segments. During T cell development, the delta chain is synthesized by a recombination event at the DNA level joining a D segment with a J segment; a V segment is then joined to the D-J gene. The alpha chain is synthesized by recombination joining a single V segment with a J segment. For both chains, the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random additional of nucleotides by terminal deoxynucleotidyltransferase. Five variable segments can be used in either alpha or delta chains and are described by TRAV/DV symbols. Several V and J segments of the alpha locus are known to be incapable of encoding a protein and are considered pseudogenes. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22533736G>T		intragenic_variant
TRAJ10	unassigned_transcript_2297	c.*179G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAJ10	ENST00000390527.1	c.*176G>T		downstream_gene_variant		6		ENSP00000451066.1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129990 AN: 152054 Hom.: 56197 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.855 AC: 130116 AN: 152172 Hom.: 56262 Cov.: 31 AF XY: 0.847 AC XY: 63033 AN XY: 74382

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.868

Alfa AF: 0.834 Hom.: 61108

Bravo AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1154155; hg19: chr14-23002684;