rs17010664

Positions:

• chr2-75049163-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001058.4(TACR1):​c.*269A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 436,248 control chromosomes in the GnomAD database, including 4,170 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 0.14 (1815 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2355 hom.)
• Consequence: TACR1 NM_001058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

Genes affected

TACR1 (HGNC:11526): (tachykinin receptor 1) This gene belongs to a gene family of tachykinin receptors. These tachykinin receptors are characterized by interactions with G proteins and contain seven hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin substance P, also referred to as neurokinin 1. The encoded protein is also involved in the mediation of phosphatidylinositol metabolism of substance P. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.*269A>G		3_prime_UTR_variant	5/5	ENST00000305249.10	NP_001049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.*269A>G		3_prime_UTR_variant	5/5	1	NM_001058.4	ENSP00000303522	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21720 AN: 152038 Hom.: 1804 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00445

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.115 AC: 32806 AN: 284092 Hom.: 2355 Cov.: 3 AF XY: 0.112 AC XY: 16351 AN XY: 145504

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.0667

Gnomad4 EAS exome AF: 0.00396

Gnomad4 SAS exome AF: 0.0423

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.143 AC: 21779 AN: 152156 Hom.: 1815 Cov.: 33 AF XY: 0.146 AC XY: 10892 AN XY: 74406

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.00465

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.110

Alfa AF: 0.134 Hom.: 400

Bravo AF: 0.144

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.68

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: rs17010664; hg19: chr2-75276290;