chr7-142802078-A-G

Variant names:

• chr7-142802078-A-G
• rs706
• ENST00000466254.1:c.404-27A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466254.1(TRBC2):​c.404-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 766,058 control chromosomes in the GnomAD database, including 52,829 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 0.36 (10525 hom., cov: 31)
  • Exomes 𝑓: 0.36 (42304 hom.)
• Consequence: TRBC2 ENST00000466254.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 11 publications found

Genes affected

TRBC2 (HGNC:12157): (T cell receptor beta constant 2) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Predicted to be involved in several processes, including activation of immune response; defense response to other organism; and phagocytosis. Predicted to be integral component of membrane. Predicted to be part of immunoglobulin complex, circulating. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRB		n.142802078A>G		intragenic_variant
TRBC2	unassigned_transcript_1404	c.404-27A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRBC2	ENST00000466254.1	c.404-27A>G		intron_variant	Intron 2 of 3	6		ENSP00000417300.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55335 AN: 151824 Hom.: 10507 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.363

GnomAD2 exomes AF: 0.342 AC: 80160 AN: 234590 AF XY: 0.340

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.306

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.359 AC: 220597 AN: 614116 Hom.: 42304 Cov.: 0 AF XY: 0.352 AC XY: 118157 AN XY: 335598

African (AFR) AF: 0.320 AC: 5653 AN: 17690

American (AMR) AF: 0.309 AC: 13498 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 6820 AN: 20984

East Asian (EAS) AF: 0.156 AC: 5621 AN: 36066

South Asian (SAS) AF: 0.211 AC: 14746 AN: 69798

European-Finnish (FIN) AF: 0.421 AC: 16359 AN: 38848

Middle Eastern (MID) AF: 0.342 AC: 1416 AN: 4142

European-Non Finnish (NFE) AF: 0.413 AC: 144488 AN: 349868

Other (OTH) AF: 0.364 AC: 11996 AN: 32986

GnomAD4 genome AF: 0.365 AC: 55389 AN: 151942 Hom.: 10525 Cov.: 31 AF XY: 0.359 AC XY: 26661 AN XY: 74270

African (AFR) AF: 0.324 AC: 13417 AN: 41424

American (AMR) AF: 0.361 AC: 5511 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1166 AN: 3464

East Asian (EAS) AF: 0.163 AC: 843 AN: 5158

South Asian (SAS) AF: 0.189 AC: 909 AN: 4816

European-Finnish (FIN) AF: 0.401 AC: 4237 AN: 10554

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.413 AC: 28069 AN: 67932

Other (OTH) AF: 0.360 AC: 758 AN: 2108

Alfa AF: 0.378 Hom.: 1114

Bravo AF: 0.362

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs706; hg19: chr7-142499762; COSMIC: COSV66585745;