14-22481502-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The variant allele was found at a frequency of 0.000152 in 151,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes
AF:
0.000152
AC:
23
AN:
151612
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
2
Hom.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.000152
AC:
23
AN:
151730
Hom.:
0
Cov.:
27
AF XY:
0.000216
AC XY:
16
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
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