rs3755459

Positions:

• chr2-75094476-G-A
• chr2-75094476-G-C

Variant summary

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

The ENST00000305249.10(TACR1):​c.584+26098C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,874 control chromosomes in the GnomAD database, including 12,543 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 0.40 (12543 hom., cov: 31)
• Consequence: TACR1 ENST00000305249.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.584+26098C>T		intron_variant		ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.584+26098C>T		intron_variant			NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.584+26098C>T		intron_variant		1	NM_001058.4	ENSP00000303522	P1
TACR1	ENST00000409848.3	c.584+26098C>T		intron_variant		1		ENSP00000386448

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61038 AN: 151756 Hom.: 12518 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61106 AN: 151874 Hom.: 12543 Cov.: 31 AF XY: 0.406 AC XY: 30129 AN XY: 74210

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.383

Alfa AF: 0.392 Hom.: 11927

Bravo AF: 0.401

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.089
DANN	Benign	0.54

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: rs3755459; hg19: chr2-75321603;