rs2242545

Variant names:

• chr14-22455202-G-A
• rs2242545

Your query was ambiguous. Multiple possible variants found:

• chr14-22455202-G-A
• chr14-22455202-G-T

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 0.258 in 762,588 control chromosomes in the GnomAD database, including 27,558 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 0.21 (4027 hom., cov: 25)
  • Exomes 𝑓: 0.27 (23531 hom.)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 5 publications found

Genes affected

TRA (HGNC:12027):

TRD (HGNC:12252):

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

TRDJ4 (HGNC:12260): (T cell receptor delta joining 4) 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514473.2. 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
	TRD-AS1	NR_148361.1		n.225+26039C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRD-AS1	ENST00000514473.2	TSL:2	n.225+26039C>T		intron	N/A
	TRDJ4	ENST00000390474.1	TSL:6	c.-49G>A		upstream_gene	N/A	ENSP00000452040.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31380 AN: 150726 Hom.: 4025 Cov.: 25

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.249 AC: 57761 AN: 231592 AF XY: 0.261

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.152

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.271 AC: 165512 AN: 611744 Hom.: 23531 Cov.: 0 AF XY: 0.277 AC XY: 92645 AN XY: 334378

African (AFR) AF: 0.0656 AC: 1155 AN: 17598

American (AMR) AF: 0.169 AC: 7353 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 5960 AN: 20902

East Asian (EAS) AF: 0.209 AC: 7523 AN: 36006

South Asian (SAS) AF: 0.342 AC: 23803 AN: 69568

European-Finnish (FIN) AF: 0.311 AC: 12031 AN: 38688

Middle Eastern (MID) AF: 0.299 AC: 1236 AN: 4130

European-Non Finnish (NFE) AF: 0.281 AC: 97925 AN: 348570

Other (OTH) AF: 0.260 AC: 8526 AN: 32842

GnomAD4 genome AF: 0.208 AC: 31398 AN: 150844 Hom.: 4027 Cov.: 25 AF XY: 0.211 AC XY: 15501 AN XY: 73632

African (AFR) AF: 0.0608 AC: 2496 AN: 41066

American (AMR) AF: 0.178 AC: 2686 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3466

East Asian (EAS) AF: 0.176 AC: 907 AN: 5152

South Asian (SAS) AF: 0.333 AC: 1581 AN: 4748

European-Finnish (FIN) AF: 0.301 AC: 3125 AN: 10372

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18884 AN: 67706

Other (OTH) AF: 0.218 AC: 454 AN: 2084

Alfa AF: 0.260 Hom.: 12281

Bravo AF: 0.191

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.015
DANN	Benign	0.29
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2242545; hg19: chr14-22924194; COSMIC: COSV66604807;