chr14-22304778-T-C

Variant names:

• chr14-22304778-T-C
• rs1467891

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 0.314 in 151,182 control chromosomes in the GnomAD database, including 8,662 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 0.31 (8662 hom., cov: 27)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 2 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 (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRD-AS1	ENST00000656379.1		n.270+96266A>G		intron	N/A
	TRAV39	ENST00000390466.1	TSL:6	c.*225T>C		downstream_gene	N/A	ENSP00000450865.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47506 AN: 151064 Hom.: 8653 Cov.: 27

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.314 AC: 47531 AN: 151182 Hom.: 8662 Cov.: 27 AF XY: 0.326 AC XY: 24088 AN XY: 73860

African (AFR) AF: 0.142 AC: 5836 AN: 41178

American (AMR) AF: 0.459 AC: 6917 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3466

East Asian (EAS) AF: 0.631 AC: 3256 AN: 5160

South Asian (SAS) AF: 0.443 AC: 2116 AN: 4774

European-Finnish (FIN) AF: 0.423 AC: 4411 AN: 10428

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 22996 AN: 67810

Other (OTH) AF: 0.319 AC: 669 AN: 2096

Alfa AF: 0.334 Hom.: 19966

Bravo AF: 0.311

Asia WGS AF: 0.523 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.5
DANN	Benign	0.81
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs1467891; hg19: chr14-22772663;