rs2009858

Positions:

• chr14-22304238-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000390466.1(TRAV39):​c.44-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 737,526 control chromosomes in the GnomAD database, including 207,291 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 (36031 hom., cov: 24)
  • Exomes 𝑓: 0.76 (171260 hom.)
• Consequence: TRAV39 ENST00000390466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

Genes affected

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]

TRAV39 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAV39	unassigned_transcript_2233	c.44-28T>C		intron_variant
TRA		n.22304238T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAV39	ENST00000390466.1	c.44-28T>C		intron_variant		6		ENSP00000450865.1
TRD-AS1	ENST00000656379.1	n.270+96806A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.674 AC: 101344 AN: 150284 Hom.: 36028 Cov.: 24

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.760 AC: 446261 AN: 587124 Hom.: 171260 Cov.: 0 AF XY: 0.763 AC XY: 243511 AN XY: 319130

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.733

GnomAD4 genome AF: 0.674 AC: 101367 AN: 150402 Hom.: 36031 Cov.: 24 AF XY: 0.681 AC XY: 50040 AN XY: 73434

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.698

Alfa AF: 0.736 Hom.: 22092

Bravo AF: 0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2009858; hg19: chr14-22772123;