rs56131962

Variant names:

• chr14-22548736-G-A
• rs56131962
• ENST00000611116.2:c.272-902G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-22548736-G-A
• chr14-22548736-G-C

Variant summary

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

The ENST00000611116.2(TRAC):​c.272-902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.82 (49661 hom., cov: 20)
• Consequence: TRAC ENST00000611116.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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 (Cadd=1.788).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22548736G>A		intragenic_variant
TRAC	unassigned_transcript_2307	c.273-902G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAC	ENST00000611116.2	c.272-902G>A		intron_variant	Intron 1 of 3	6		ENSP00000480116.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 119697 AN: 145284 Hom.: 49631 Cov.: 20

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.827

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.824 AC: 119763 AN: 145362 Hom.: 49661 Cov.: 20 AF XY: 0.817 AC XY: 57564 AN XY: 70486

African (AFR) AF: 0.885 AC: 34875 AN: 39386

American (AMR) AF: 0.810 AC: 11745 AN: 14502

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2874 AN: 3432

East Asian (EAS) AF: 0.399 AC: 1863 AN: 4672

South Asian (SAS) AF: 0.760 AC: 3435 AN: 4520

European-Finnish (FIN) AF: 0.734 AC: 6615 AN: 9016

Middle Eastern (MID) AF: 0.828 AC: 227 AN: 274

European-Non Finnish (NFE) AF: 0.835 AC: 55682 AN: 66698

Other (OTH) AF: 0.845 AC: 1666 AN: 1972

Alfa AF: 0.838 Hom.: 3797

Bravo AF: 0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.8
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs56131962; hg19: -;