14-22533736-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204
Variant links:
Genes affected
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
TRAJ10unassigned_transcript_2297 c.*179G>T downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRAJ10ENST00000390527.1 linkc.*176G>T downstream_gene_variant 6 ENSP00000451066.1 A0N4Z7

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1154155; hg19: chr14-23002684; API