rs12713828

Positions:

• chr2-75048954-G-A

Variant summary

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

The NM_001058.4(TACR1):​c.*478C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 155,870 control chromosomes in the GnomAD database, including 12,490 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 0.39 (12181 hom., cov: 32)
  • Exomes 𝑓: 0.37 (309 hom.)
• Consequence: TACR1 NM_001058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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 (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.*478C>T		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.*478C>T		3_prime_UTR_variant	5/5	1	NM_001058.4	ENSP00000303522.4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59836 AN: 151976 Hom.: 12181 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.375 AC: 1415 AN: 3778 Hom.: 309 Cov.: 0 AF XY: 0.373 AC XY: 708 AN XY: 1898

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.394 AC: 59854 AN: 152092 Hom.: 12181 Cov.: 32 AF XY: 0.388 AC XY: 28845 AN XY: 74368

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.422

Alfa AF: 0.439 Hom.: 14710

Bravo AF: 0.400

Asia WGS AF: 0.355 AC: 1235 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	2.5
DANN	Benign	0.46

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: rs12713828; hg19: chr2-75276081;