rs2009858

Variant names:

• chr14-22304238-T-C
• rs2009858
• ENST00000390466.1:c.44-28T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

TRA (HGNC:12027):

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390466.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAV39	ENST00000390466.1	TSL:6	c.44-28T>C		intron	N/A	ENSP00000450865.1
	TRD-AS1	ENST00000656379.1		n.270+96806A>G		intron	N/A

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

African (AFR) AF: 0.427 AC: 7298 AN: 17072

American (AMR) AF: 0.794 AC: 31522 AN: 39680

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 13804 AN: 20394

East Asian (EAS) AF: 0.852 AC: 30160 AN: 35392

South Asian (SAS) AF: 0.792 AC: 52395 AN: 66114

European-Finnish (FIN) AF: 0.811 AC: 30394 AN: 37464

Middle Eastern (MID) AF: 0.630 AC: 2585 AN: 4100

European-Non Finnish (NFE) AF: 0.760 AC: 254613 AN: 334854

Other (OTH) AF: 0.733 AC: 23490 AN: 32054

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

African (AFR) AF: 0.424 AC: 17261 AN: 40752

American (AMR) AF: 0.773 AC: 11572 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2352 AN: 3456

East Asian (EAS) AF: 0.869 AC: 4478 AN: 5156

South Asian (SAS) AF: 0.777 AC: 3677 AN: 4730

European-Finnish (FIN) AF: 0.811 AC: 8404 AN: 10364

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51434 AN: 67688

Other (OTH) AF: 0.698 AC: 1455 AN: 2086

Alfa AF: 0.736 Hom.: 24167

Bravo AF: 0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs2009858; hg19: chr14-22772123;