rs1263648

Variant names:

• chr14-22548784-G-A
• rs1263648
• ENST00000611116.2:c.272-854G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-22548784-G-A
• chr14-22548784-G-C
• chr14-22548784-G-T

Variant summary

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

The ENST00000611116.2(TRAC):​c.272-854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 149,688 control chromosomes in the GnomAD database, including 52,979 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 0.84 (52979 hom., cov: 24)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 1 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=-1.0).
• 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 rank	MANE	Protein	UniProt
TRA		n.22548784G>A		intragenic_variant
TRAC	unassigned_transcript_2307	c.273-854G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAC	ENST00000611116.2	c.272-854G>A		intron_variant	Intron 1 of 3	6		ENSP00000480116.1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 124923 AN: 149572 Hom.: 52914 Cov.: 24

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.835 AC: 125046 AN: 149688 Hom.: 52979 Cov.: 24 AF XY: 0.826 AC XY: 60170 AN XY: 72880

African (AFR) AF: 0.945 AC: 38712 AN: 40962

American (AMR) AF: 0.809 AC: 12215 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2848 AN: 3434

East Asian (EAS) AF: 0.400 AC: 1966 AN: 4910

South Asian (SAS) AF: 0.756 AC: 3564 AN: 4716

European-Finnish (FIN) AF: 0.710 AC: 7222 AN: 10170

Middle Eastern (MID) AF: 0.813 AC: 231 AN: 284

European-Non Finnish (NFE) AF: 0.830 AC: 55757 AN: 67160

Other (OTH) AF: 0.847 AC: 1744 AN: 2060

Alfa AF: 0.844 Hom.: 5872

Bravo AF: 0.843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1263648; hg19: chr14-23017730;