chr2-75066030-A-G

Variant names:

• chr2-75066030-A-G
• rs11688000
• NM_001058.4:c.585-12275T>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.585-12275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,076 control chromosomes in the GnomAD database, including 9,506 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 0.34 (9506 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.585-12275T>C		intron_variant	Intron 2 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.585-12275T>C		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.585-12275T>C		intron_variant	Intron 2 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.585-12275T>C		intron_variant	Intron 2 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52209 AN: 151958 Hom.: 9500 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.344 AC: 52242 AN: 152076 Hom.: 9506 Cov.: 32 AF XY: 0.347 AC XY: 25793 AN XY: 74340

African (AFR) AF: 0.227 AC: 9412 AN: 41484

American (AMR) AF: 0.458 AC: 6998 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1229 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2184 AN: 5178

South Asian (SAS) AF: 0.399 AC: 1916 AN: 4808

European-Finnish (FIN) AF: 0.353 AC: 3732 AN: 10562

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25426 AN: 67966

Other (OTH) AF: 0.363 AC: 767 AN: 2112

Alfa AF: 0.372 Hom.: 21419

Bravo AF: 0.349

Asia WGS AF: 0.397 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.46
PhyloP100		-0.29
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: rs11688000; hg19: chr2-75293157;