2-75080526-T-C

Variant names:

• chr2-75080526-T-C
• rs3771810
• NM_001058.4:c.585-26771A>G

Variant summary

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

The NM_001058.4(TACR1):​c.585-26771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,078 control chromosomes in the GnomAD database, including 4,310 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 0.22 (4310 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.585-26771A>G		intron_variant	Intron 2 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.585-26771A>G		intron_variant	Intron 2 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.585-26771A>G		intron_variant	Intron 2 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.585-26771A>G		intron_variant	Intron 2 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32902 AN: 151958 Hom.: 4286 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.217 AC: 32979 AN: 152078 Hom.: 4310 Cov.: 32 AF XY: 0.219 AC XY: 16250 AN XY: 74346

African (AFR) AF: 0.326 AC: 13520 AN: 41448

American (AMR) AF: 0.331 AC: 5045 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1232 AN: 5180

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1362 AN: 10598

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9467 AN: 67994

Other (OTH) AF: 0.215 AC: 454 AN: 2116

Alfa AF: 0.213 Hom.: 896

Bravo AF: 0.240

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.71
PhyloP100		-3.3
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: rs3771810; hg19: chr2-75307653;