14-22548819-T-C

Variant names:

• chr14-22548819-T-C
• rs1263651
• ENST00000611116.2:c.272-819T>C

Variant summary

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

The ENST00000611116.2(TRAC):​c.272-819T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 150,780 control chromosomes in the GnomAD database, including 48,504 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 0.79 (48504 hom., cov: 27)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen

TRA (HGNC:12027):

ACMG classification

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

• BP4: Computational evidence support a benign effect (Cadd=2.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAC	ENST00000611116.2	TSL:6	c.272-819T>C		intron	N/A	ENSP00000480116.1	A0A5H1ZRS8

Frequencies

GnomAD3 genomes AF: 0.794 AC: 119677 AN: 150660 Hom.: 48451 Cov.: 27

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.794 AC: 119784 AN: 150780 Hom.: 48504 Cov.: 27 AF XY: 0.783 AC XY: 57554 AN XY: 73528

African (AFR) AF: 0.855 AC: 35283 AN: 41276

American (AMR) AF: 0.785 AC: 11930 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2782 AN: 3434

East Asian (EAS) AF: 0.280 AC: 1438 AN: 5136

South Asian (SAS) AF: 0.656 AC: 3118 AN: 4750

European-Finnish (FIN) AF: 0.702 AC: 7312 AN: 10418

Middle Eastern (MID) AF: 0.772 AC: 224 AN: 290

European-Non Finnish (NFE) AF: 0.820 AC: 55200 AN: 67298

Other (OTH) AF: 0.818 AC: 1708 AN: 2088

Alfa AF: 0.761 Hom.: 2206

Bravo AF: 0.802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.7
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs1263651;