rs227860

Variant names:

• chr14-22481502-T-A
• rs227860

Your query was ambiguous. Multiple possible variants found:

• chr14-22481502-T-A
• chr14-22481502-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• Publications: 1 publications found

Genes affected

TRA (HGNC:12027):

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]

ACMG classification

Our verdict: Benign. The variant received -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-AS1	NR_148361.1	n.108-144A>T		intron_variant	Intron 1 of 4
TRAJ55	unassigned_transcript_2252	n.-195T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000514473.2	n.108-144A>T		intron_variant	Intron 1 of 2	2
TRD-AS1	ENST00000556777.2	n.445-144A>T		intron_variant	Intron 1 of 3	3
TRAJ55	ENST00000509135.1	n.-195T>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20352 AN: 151538 Hom.: 1813 Cov.: 27

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.134 AC: 20348 AN: 151656 Hom.: 1815 Cov.: 27 AF XY: 0.139 AC XY: 10271 AN XY: 74102

African (AFR) AF: 0.0950 AC: 3923 AN: 41294

American (AMR) AF: 0.0955 AC: 1448 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2511 AN: 5158

South Asian (SAS) AF: 0.235 AC: 1128 AN: 4800

European-Finnish (FIN) AF: 0.174 AC: 1830 AN: 10524

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8585 AN: 67926

Other (OTH) AF: 0.118 AC: 250 AN: 2112

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
PhyloP100		0.97

Splicing

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

Other links and lift over

dbSNP: rs227860; hg19: chr14-22950491;