ENST00000621184.1:c.85C>G

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRBV12-5	unassigned_transcript_1368	c.85C>G	p.His29Asp	missense_variant	Exon 2 of 2
TRB		n.142581165C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRBV12-5	ENST00000621184.1	c.85C>G	p.His29Asp	missense_variant	Exon 2 of 2	6		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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Keratoconus Uncertain:1

Apr 01, 2023

Institute of Human Genetics, Polish Academy of Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

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; hg19: -;