rs881

Positions:

• chr2-75049302-C-G

Variant summary

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

The NM_001058.4(TACR1):​c.*130G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,016,610 control chromosomes in the GnomAD database, including 18,187 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 (2779 hom., cov: 33)
  • Exomes 𝑓: 0.18 (15408 hom.)
• Consequence: TACR1 NM_001058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.*130G>C		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.*130G>C		3_prime_UTR_variant	5/5	1	NM_001058.4	ENSP00000303522.4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28274 AN: 152074 Hom.: 2780 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.182 AC: 157309 AN: 864418 Hom.: 15408 Cov.: 11 AF XY: 0.187 AC XY: 81281 AN XY: 434074

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.186 AC: 28289 AN: 152192 Hom.: 2779 Cov.: 33 AF XY: 0.187 AC XY: 13944 AN XY: 74408

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.213

Alfa AF: 0.182 Hom.: 350

Bravo AF: 0.191

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs881; hg19: chr2-75276429; COSMIC: COSV59480908; COSMIC: COSV59480908;