rs3755458

Variant names:

• chr2-75064394-C-T
• rs3755458
• NM_001058.4:c.585-10639G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001058.4(TACR1):​c.585-10639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,128 control chromosomes in the GnomAD database, including 1,256 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 0.11 (1256 hom., cov: 33)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	NM_001058.4	MANE Select	c.585-10639G>A		intron	N/A	NP_001049.1
	TACR1	NM_015727.3		c.585-10639G>A		intron	N/A	NP_056542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	ENST00000305249.10	TSL:1 MANE Select	c.585-10639G>A		intron	N/A	ENSP00000303522.4
	TACR1	ENST00000409848.3	TSL:1	c.585-10639G>A		intron	N/A	ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16712 AN: 152010 Hom.: 1252 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.110 AC: 16726 AN: 152128 Hom.: 1256 Cov.: 33 AF XY: 0.111 AC XY: 8270 AN XY: 74386

African (AFR) AF: 0.147 AC: 6110 AN: 41496

American (AMR) AF: 0.155 AC: 2371 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1599 AN: 5174

South Asian (SAS) AF: 0.161 AC: 778 AN: 4820

European-Finnish (FIN) AF: 0.0423 AC: 447 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4721 AN: 68000

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0863 Hom.: 2235

Bravo AF: 0.118

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.79
PhyloP100		-0.069
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3755458; hg19: chr2-75291521;