rs8192620

Positions:

• chr6-132645140-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138327.4(TAAR1):​c.864A>G​(p.Val288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,680 control chromosomes in the GnomAD database, including 42,071 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 0.19 (3082 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38989 hom.)
• Consequence: TAAR1 NM_138327.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

Genes affected

TAAR1 (HGNC:17734): (trace amine associated receptor 1) The protein encoded by this gene is a G-protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to beta-phenylethylamine, p-tyramine, octopamine, and tryptamine. While primarily functioning in neurologic systems, there is evidence that this gene is involved in blood cell and immunologic functions as well. This gene is thought to be intronless. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.886 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR1	NM_138327.4	c.864A>G	p.Val288=	synonymous_variant	2/2	ENST00000275216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR1	ENST00000275216.3	c.864A>G	p.Val288=	synonymous_variant	2/2		NM_138327.4	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29321 AN: 151868 Hom.: 3079 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.220 AC: 54971 AN: 250130 Hom.: 6412 AF XY: 0.223 AC XY: 30204 AN XY: 135168

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.228 AC: 332775 AN: 1460694 Hom.: 38989 Cov.: 34 AF XY: 0.228 AC XY: 165411 AN XY: 726606

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.193 AC: 29336 AN: 151986 Hom.: 3082 Cov.: 32 AF XY: 0.194 AC XY: 14426 AN XY: 74300

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.180

Alfa AF: 0.211 Hom.: 3879

Bravo AF: 0.187

Asia WGS AF: 0.282 AC: 978 AN: 3478

EpiCase AF: 0.232

EpiControl AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192620; hg19: chr6-132966279; COSMIC: COSV51588625;