rs1569297

Variant names:

• chr14-22304710-T-C
• rs1569297

Variant summary

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

The variant allele was found at a frequency of 0.674 in 150,886 control chromosomes in the GnomAD database, including 36,189 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 0.67 (36189 hom., cov: 26)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 1 publications found

Genes affected

TRA (HGNC:12027):

TRD-AS1 (HGNC:56197): (TRD antisense RNA 1)

TRAV39 (HGNC:12139): (T cell receptor alpha variable 39) 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (Cadd=12.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000656379.1. 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
	TRD-AS1	ENST00000656379.1		n.270+96334A>G		intron	N/A
	TRAV39	ENST00000390466.1	TSL:6	c.*157T>C		downstream_gene	N/A	ENSP00000450865.1	A0A0B4J263

Frequencies

GnomAD3 genomes AF: 0.675 AC: 101738 AN: 150768 Hom.: 36187 Cov.: 26

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.674 AC: 101762 AN: 150886 Hom.: 36189 Cov.: 26 AF XY: 0.682 AC XY: 50271 AN XY: 73678

African (AFR) AF: 0.425 AC: 17359 AN: 40850

American (AMR) AF: 0.772 AC: 11621 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3466

East Asian (EAS) AF: 0.868 AC: 4497 AN: 5178

South Asian (SAS) AF: 0.778 AC: 3725 AN: 4786

European-Finnish (FIN) AF: 0.812 AC: 8461 AN: 10418

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51546 AN: 67842

Other (OTH) AF: 0.697 AC: 1462 AN: 2098

Alfa AF: 0.713 Hom.: 6675

Bravo AF: 0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	13
PhyloP100		0.48

Splicing

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

Other links and lift over

dbSNP: rs1569297;