chr14-22548808-G-A

Variant names:

• chr14-22548808-G-A
• rs1263650
• ENST00000611116.2:c.272-830G>A

Variant summary

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

The ENST00000611116.2(TRAC):​c.272-830G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 150,434 control chromosomes in the GnomAD database, including 43,060 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 0.75 (43060 hom., cov: 27)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 0 publications found

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]

TRAC Gene-Disease associations (from GenCC):

• TCR-alpha-beta-positive T-cell deficiency

  Inheritance: AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

TRA (HGNC:12027):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.12).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAC	ENST00000611116.2	TSL:6	c.272-830G>A		intron	N/A	ENSP00000480116.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 112556 AN: 150316 Hom.: 43024 Cov.: 27

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.749 AC: 112642 AN: 150434 Hom.: 43060 Cov.: 27 AF XY: 0.739 AC XY: 54159 AN XY: 73316

African (AFR) AF: 0.699 AC: 28750 AN: 41120

American (AMR) AF: 0.765 AC: 11609 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2778 AN: 3430

East Asian (EAS) AF: 0.274 AC: 1405 AN: 5130

South Asian (SAS) AF: 0.673 AC: 3207 AN: 4764

European-Finnish (FIN) AF: 0.702 AC: 7282 AN: 10370

Middle Eastern (MID) AF: 0.750 AC: 216 AN: 288

European-Non Finnish (NFE) AF: 0.818 AC: 54973 AN: 67174

Other (OTH) AF: 0.786 AC: 1633 AN: 2078

Alfa AF: 0.783 Hom.: 4763

Bravo AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
PhyloP100		-3.6

Splicing

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

Other links and lift over

dbSNP: rs1263650; hg19: chr14-23017754;