2-75155265-T-C

Variant names:

• chr2-75155265-T-C
• rs3755468
• NM_001058.4:c.390-34497A>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.390-34497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,016 control chromosomes in the GnomAD database, including 26,504 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 0.59 (26504 hom., cov: 31)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.390-34497A>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.390-34497A>G		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.390-34497A>G		intron_variant	Intron 1 of 3	1		ENSP00000386448.3
ENSG00000270571	ENST00000604271.2	n.206+694T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89037 AN: 151898 Hom.: 26481 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.586 AC: 89109 AN: 152016 Hom.: 26504 Cov.: 31 AF XY: 0.578 AC XY: 42960 AN XY: 74308

African (AFR) AF: 0.667 AC: 27632 AN: 41438

American (AMR) AF: 0.593 AC: 9069 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2707 AN: 5164

South Asian (SAS) AF: 0.526 AC: 2531 AN: 4812

European-Finnish (FIN) AF: 0.437 AC: 4616 AN: 10568

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38509 AN: 67962

Other (OTH) AF: 0.602 AC: 1271 AN: 2112

Alfa AF: 0.579 Hom.: 32370

Bravo AF: 0.606

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.39
PhyloP100		-1.1
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: rs3755468; hg19: chr2-75382391;