6-132645209-G-A

Position:

• chr6-132645209-G-A

Variant summary

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

The NM_138327.4(TAAR1):​c.795C>T​(p.Cys265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 1,613,326 control chromosomes in the GnomAD database, including 3,271 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 0.062 (336 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2935 hom.)
• Consequence: TAAR1 NM_138327.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.754 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR1	NM_138327.4	c.795C>T	p.Cys265=	synonymous_variant	2/2	ENST00000275216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR1	ENST00000275216.3	c.795C>T	p.Cys265=	synonymous_variant	2/2		NM_138327.4	P1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9437 AN: 151956 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0666 AC: 16703 AN: 250760 Hom.: 653 AF XY: 0.0666 AC XY: 9020 AN XY: 135526

Gnomad AFR exome AF: 0.0605

Gnomad AMR exome AF: 0.0845

Gnomad ASJ exome AF: 0.0200

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.0848

Gnomad FIN exome AF: 0.0793

Gnomad NFE exome AF: 0.0525

Gnomad OTH exome AF: 0.0557

GnomAD4 exome AF: 0.0599 AC: 87502 AN: 1461252 Hom.: 2935 Cov.: 33 AF XY: 0.0605 AC XY: 43966 AN XY: 726922

Gnomad4 AFR exome AF: 0.0594

Gnomad4 AMR exome AF: 0.0861

Gnomad4 ASJ exome AF: 0.0194

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0860

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.0551

Gnomad4 OTH exome AF: 0.0614

GnomAD4 genome AF: 0.0622 AC: 9455 AN: 152074 Hom.: 336 Cov.: 32 AF XY: 0.0647 AC XY: 4807 AN XY: 74340

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0533 Hom.: 302

Bravo AF: 0.0594

Asia WGS AF: 0.0810 AC: 283 AN: 3476

EpiCase AF: 0.0518

EpiControl AF: 0.0526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.1
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs8192619; hg19: chr6-132966348;