rs2193409

Variant names:

• chr2-75188293-T-C
• rs2193409
• NM_001058.4:c.389+10253A>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.389+10253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,150 control chromosomes in the GnomAD database, including 11,559 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 0.38 (11559 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 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 = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.389+10253A>G		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+10253A>G		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.389+10253A>G		intron_variant	Intron 1 of 3	1		ENSP00000386448.3
ENSG00000270571	ENST00000604271.2	n.1782T>C		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57796 AN: 152032 Hom.: 11556 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.385

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.380 AC: 57839 AN: 152150 Hom.: 11559 Cov.: 33 AF XY: 0.380 AC XY: 28289 AN XY: 74380

African (AFR) AF: 0.508 AC: 21070 AN: 41498

American (AMR) AF: 0.385 AC: 5887 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 921 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2032 AN: 5162

South Asian (SAS) AF: 0.352 AC: 1701 AN: 4826

European-Finnish (FIN) AF: 0.308 AC: 3267 AN: 10596

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21850 AN: 67996

Other (OTH) AF: 0.383 AC: 808 AN: 2112

Alfa AF: 0.350 Hom.: 15811

Bravo AF: 0.395

Asia WGS AF: 0.387 AC: 1342 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	7.8
DANN	Benign	0.72
PhyloP100		-0.13
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: rs2193409; hg19: chr2-75415419;