chr14-22548589-G-T

Variant names:

• chr14-22548589-G-T
• rs1263646
• ENST00000611116.2:c.271+811G>T

Variant summary

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

The ENST00000611116.2(TRAC):​c.271+811G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 149,368 control chromosomes in the GnomAD database, including 51,796 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 (51796 hom., cov: 24)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 8 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=0.924).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 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.271+811G>T		intron	N/A	ENSP00000480116.1	A0A5H1ZRS8

Frequencies

GnomAD3 genomes AF: 0.829 AC: 123715 AN: 149260 Hom.: 51753 Cov.: 24

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.829 AC: 123809 AN: 149368 Hom.: 51796 Cov.: 24 AF XY: 0.824 AC XY: 59893 AN XY: 72724

African (AFR) AF: 0.888 AC: 35885 AN: 40402

American (AMR) AF: 0.801 AC: 11977 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2915 AN: 3460

East Asian (EAS) AF: 0.473 AC: 2357 AN: 4980

South Asian (SAS) AF: 0.768 AC: 3635 AN: 4734

European-Finnish (FIN) AF: 0.797 AC: 7869 AN: 9876

Middle Eastern (MID) AF: 0.817 AC: 237 AN: 290

European-Non Finnish (NFE) AF: 0.833 AC: 56383 AN: 67702

Other (OTH) AF: 0.851 AC: 1752 AN: 2058

Alfa AF: 0.833 Hom.: 8945

Bravo AF: 0.830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.92
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs1263646;