rs17229

Variant names:

• chr7-142581165-C-G
• rs17229
• ENST00000621184.1:c.85C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000621184.1(TRBV12-5):​c.85C>G​(p.His29Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 214,206 control chromosomes in the GnomAD database, including 23,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (15747 hom., cov: 30)
  • Exomes 𝑓: 0.48 (7921 hom.)
• Consequence: TRBV12-5 ENST00000621184.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.568
• Publications: 7 publications found

Genes affected

TRBV12-5 (HGNC:12187): (T cell receptor beta variable 12-5) Predicted to be involved in cell surface receptor signaling pathway. Predicted to be part of T cell receptor complex. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=17.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621184.1. 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
	TRBV12-5	ENST00000621184.1	TSL:6	c.85C>G	p.His29Asp	missense	Exon 2 of 2	ENSP00000479506.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63565 AN: 151712 Hom.: 15759 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.483 AC: 30111 AN: 62378 Hom.: 7921 Cov.: 0 AF XY: 0.494 AC XY: 18278 AN XY: 36972

African (AFR) AF: 0.166 AC: 314 AN: 1886

American (AMR) AF: 0.244 AC: 2196 AN: 9004

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 493 AN: 954

East Asian (EAS) AF: 0.598 AC: 2371 AN: 3964

South Asian (SAS) AF: 0.455 AC: 3198 AN: 7024

European-Finnish (FIN) AF: 0.634 AC: 2649 AN: 4180

Middle Eastern (MID) AF: 0.417 AC: 30 AN: 72

European-Non Finnish (NFE) AF: 0.533 AC: 17556 AN: 32920

Other (OTH) AF: 0.549 AC: 1304 AN: 2374

GnomAD4 genome AF: 0.419 AC: 63569 AN: 151828 Hom.: 15747 Cov.: 30 AF XY: 0.423 AC XY: 31393 AN XY: 74174

African (AFR) AF: 0.168 AC: 6943 AN: 41426

American (AMR) AF: 0.338 AC: 5156 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3208 AN: 5158

South Asian (SAS) AF: 0.463 AC: 2220 AN: 4792

European-Finnish (FIN) AF: 0.653 AC: 6867 AN: 10512

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36049 AN: 67900

Other (OTH) AF: 0.430 AC: 910 AN: 2114

Alfa AF: 0.432 Hom.: 1479

Bravo AF: 0.382

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Keratoconus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
CADD	Benign	17
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs17229;