dbSNP rs4435168: TRA:n.22281859T>C (chr14-22281859-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The variant allele was found at a frequency of 0.102 in 710,752 control chromosomes in the GnomAD database, including 4,395 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 0.081 ( 648 hom., cov: 25)

Exomes 𝑓: 0.11 ( 3747 hom. )

Consequence

TRA
intragenic

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Variant links:

Genes affected

TRA (HGNC:12027):

TRA links:

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

TRD-AS1 links:

TRAV38-2DV8 (HGNC:12138): (T cell receptor alpha variable 38-2/delta variable 8) 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]

TRAV38-2DV8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22281859T>C		intragenic_variant
TRAV38-2DV8	unassigned_transcript_2232	c.*114T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000656379.1 link	n.271-80477A>G		intron_variant	Intron 3 of 3
TRAV38-2DV8	ENST00000390465.2 link	c.*111T>C		downstream_gene_variant		6		ENSP00000452332.1		A0JD32

Frequencies

GnomAD3 genomes

AF:

0.0813

AC:

12221

AN:

150302

Hom.:

644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0843

Gnomad EAS

AF:

0.0751

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.0852

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0979

GnomAD3 exomes

AF:

0.116

AC:

18020

AN:

154860

Hom.:

1207

AF XY:

0.119

AC XY:

10031

AN XY:

84574

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.0822

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.0841

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.108

AC:

60357

AN:

560332

Hom.:

3747

Cov.:

AF XY:

0.111

AC XY:

33892

AN XY:

304934

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.0899

Gnomad4 EAS exome

AF:

0.0647

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.0913

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0814

AC:

12239

AN:

150420

Hom.:

648

Cov.:

AF XY:

0.0816

AC XY:

5992

AN XY:

73428

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0843

Gnomad4 EAS

AF:

0.0758

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.0852

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.0988

Alfa

AF:

0.104

Hom.:

1224

Bravo

AF:

0.0821

Asia WGS

AF:

0.100

AC:

348

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.81

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over