rs227860

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 0.134 in 151,656 control chromosomes in the GnomAD database, including 1,815 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 0.13 ( 1815 hom., cov: 27)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TRA
intragenic

Scores

1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.967
Variant links:
Genes affected
TRD-AS1 (HGNC:56197): (TRD antisense RNA 1)
TRAJ55 (HGNC:12087): (T cell receptor alpha joining 55 (pseudogene)) 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=-0.83).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRA n.22481502T>A intragenic_variant
TRD-AS1NR_148361.1 linkn.108-144A>T intron_variant Intron 1 of 4
TRAJ55unassigned_transcript_2252 n.-195T>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRD-AS1ENST00000514473.2 linkn.108-144A>T intron_variant Intron 1 of 2 2
TRD-AS1ENST00000556777.2 linkn.445-144A>T intron_variant Intron 1 of 3 3
TRAJ55ENST00000509135.1 linkn.-195T>A upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.134
AC:
20352
AN:
151538
Hom.:
1813
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.0950
Gnomad AMI
AF:
0.259
Gnomad AMR
AF:
0.0956
Gnomad ASJ
AF:
0.115
Gnomad EAS
AF:
0.486
Gnomad SAS
AF:
0.237
Gnomad FIN
AF:
0.174
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.126
Gnomad OTH
AF:
0.119
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.134
AC:
20348
AN:
151656
Hom.:
1815
Cov.:
27
AF XY:
0.139
AC XY:
10271
AN XY:
74102
show subpopulations
Gnomad4 AFR
AF:
0.0950
Gnomad4 AMR
AF:
0.0955
Gnomad4 ASJ
AF:
0.115
Gnomad4 EAS
AF:
0.487
Gnomad4 SAS
AF:
0.235
Gnomad4 FIN
AF:
0.174
Gnomad4 NFE
AF:
0.126
Gnomad4 OTH
AF:
0.118
Alfa
AF:
0.0586
Hom.:
62
Bravo
AF:
0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
9.2

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: rs227860; hg19: chr14-22950491; API