rs1263649

Positions:

• chr14-22548793-A-G
• chr14-22548793-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611116.2(TRAC):​c.274-845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 150,254 control chromosomes in the GnomAD database, including 53,115 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 0.83 (53115 hom., cov: 25)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

Genes affected

TRAC (HGNC:12029): (T cell receptor alpha constant) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAC	ENST00000611116.2	c.274-845A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 125178 AN: 150142 Hom.: 53050 Cov.: 25

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.834 AC: 125302 AN: 150254 Hom.: 53115 Cov.: 25 AF XY: 0.824 AC XY: 60332 AN XY: 73216

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.849

Alfa AF: 0.845 Hom.: 6663

Bravo AF: 0.843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1263649; hg19: chr14-23017739;