rs733905

Variant names:

• chr7-38340845-T-C
• rs733905
• unassigned_transcript_1234:c.208A>G

Variant summary

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

The ENST00000000000(TRGV6):​c.208A>G​(p.Ile70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 525,722 control chromosomes in the GnomAD database, including 7,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (4256 hom., cov: 28)
  • Exomes 𝑓: 0.11 (3029 hom.)
• Consequence: TRGV6 ENST00000000000 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.56
• Publications: 8 publications found

Genes affected

TRGV6 (HGNC:12292): (T cell receptor gamma variable 6 (pseudogene))

TRG (HGNC:12271):

TRG-AS1 (HGNC:48974): (T cell receptor gamma locus antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRGV6	unassigned_transcript_1234	c.208A>G	p.Ile70Val	missense_variant	Exon 2 of 2
TRG		n.38340845T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRGV6	ENST00000417928.1	n.154A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
TRG-AS1	ENST00000685545.1	n.396+4019T>C		intron_variant	Intron 2 of 3
TRG-AS1	ENST00000687516.1	n.541-1411T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28855 AN: 151482 Hom.: 4250 Cov.: 28

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.107 AC: 40084 AN: 374122 Hom.: 3029 Cov.: 0 AF XY: 0.104 AC XY: 22296 AN XY: 214500

African (AFR) AF: 0.426 AC: 4470 AN: 10486

American (AMR) AF: 0.0871 AC: 3180 AN: 36496

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 1699 AN: 11930

East Asian (EAS) AF: 0.106 AC: 1456 AN: 13752

South Asian (SAS) AF: 0.0762 AC: 5154 AN: 67604

European-Finnish (FIN) AF: 0.0357 AC: 656 AN: 18382

Middle Eastern (MID) AF: 0.233 AC: 545 AN: 2344

European-Non Finnish (NFE) AF: 0.107 AC: 20909 AN: 196150

Other (OTH) AF: 0.119 AC: 2015 AN: 16978

GnomAD4 genome AF: 0.191 AC: 28882 AN: 151600 Hom.: 4256 Cov.: 28 AF XY: 0.183 AC XY: 13593 AN XY: 74104

African (AFR) AF: 0.415 AC: 17080 AN: 41120

American (AMR) AF: 0.142 AC: 2165 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3464

East Asian (EAS) AF: 0.127 AC: 655 AN: 5164

South Asian (SAS) AF: 0.0777 AC: 373 AN: 4798

European-Finnish (FIN) AF: 0.0292 AC: 309 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7332 AN: 67936

Other (OTH) AF: 0.184 AC: 387 AN: 2102

Alfa AF: 0.144 Hom.: 6799

Bravo AF: 0.213

Asia WGS AF: 0.117 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.048
DANN	Benign	0.30
PhyloP100		-5.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs733905; hg19: chr7-38380446; COSMIC: COSV68900407;