chr2-75174939-A-G

Variant names:

• chr2-75174939-A-G
• rs12477554
• NM_001058.4:c.389+23607T>C

Variant summary

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

The NM_001058.4(TACR1):​c.389+23607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,960 control chromosomes in the GnomAD database, including 26,119 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 0.58 (26119 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 8 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]

ENSG00000270571 (HGNC:58209):

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 (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.389+23607T>C		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.389+23607T>C		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.389+23607T>C		intron_variant	Intron 1 of 3	1		ENSP00000386448.3
ENSG00000270571	ENST00000604271.2	n.319-11891A>G		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88161 AN: 151842 Hom.: 26087 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.581 AC: 88254 AN: 151960 Hom.: 26119 Cov.: 32 AF XY: 0.582 AC XY: 43203 AN XY: 74242

African (AFR) AF: 0.611 AC: 25325 AN: 41428

American (AMR) AF: 0.532 AC: 8121 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1671 AN: 5158

South Asian (SAS) AF: 0.533 AC: 2563 AN: 4806

European-Finnish (FIN) AF: 0.651 AC: 6867 AN: 10552

Middle Eastern (MID) AF: 0.528 AC: 153 AN: 290

European-Non Finnish (NFE) AF: 0.580 AC: 39423 AN: 67954

Other (OTH) AF: 0.564 AC: 1193 AN: 2114

Alfa AF: 0.572 Hom.: 68455

Bravo AF: 0.571

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-0.25
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: rs12477554; hg19: chr2-75402065;