rs6572493

Variant names:

• chr14-22503969-A-G
• rs6572493

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 0.535 in 151,664 control chromosomes in the GnomAD database, including 22,804 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 0.54 (22804 hom., cov: 29)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 publications found

Genes affected

TRA (HGNC:12027):

TRAJ37 (HGNC:12067): (T cell receptor alpha joining 37) 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22503969A>G		intragenic_variant
TRAJ37	unassigned_transcript_2270	c.*161A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAJ37	ENST00000612375.1	c.*155A>G		downstream_gene_variant		6		ENSP00000483197.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81152 AN: 151542 Hom.: 22783 Cov.: 29

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.535 AC: 81191 AN: 151664 Hom.: 22804 Cov.: 29 AF XY: 0.541 AC XY: 40072 AN XY: 74076

African (AFR) AF: 0.352 AC: 14563 AN: 41324

American (AMR) AF: 0.637 AC: 9684 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2075 AN: 3464

East Asian (EAS) AF: 0.530 AC: 2736 AN: 5158

South Asian (SAS) AF: 0.647 AC: 3112 AN: 4810

European-Finnish (FIN) AF: 0.645 AC: 6754 AN: 10476

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40435 AN: 67904

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.576 Hom.: 82529

Bravo AF: 0.525

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.70
PhyloP100		-1.5
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6572493; hg19: chr14-22972955;