2-75121920-C-T

Variant names:

• chr2-75121920-C-T
• rs7588326
• NM_001058.4:c.390-1152G>A

Variant summary

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

The NM_001058.4(TACR1):​c.390-1152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,946 control chromosomes in the GnomAD database, including 18,550 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 0.48 (18550 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.390-1152G>A		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.390-1152G>A		intron_variant	Intron 1 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.390-1152G>A		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.390-1152G>A		intron_variant	Intron 1 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73394 AN: 151828 Hom.: 18546 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.483 AC: 73424 AN: 151946 Hom.: 18550 Cov.: 32 AF XY: 0.474 AC XY: 35223 AN XY: 74254

African (AFR) AF: 0.488 AC: 20228 AN: 41422

American (AMR) AF: 0.390 AC: 5965 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3470

East Asian (EAS) AF: 0.109 AC: 563 AN: 5168

South Asian (SAS) AF: 0.319 AC: 1534 AN: 4808

European-Finnish (FIN) AF: 0.508 AC: 5355 AN: 10536

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36535 AN: 67946

Other (OTH) AF: 0.463 AC: 977 AN: 2112

Alfa AF: 0.490 Hom.: 8718

Bravo AF: 0.473

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.77
PhyloP100		0.61
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: rs7588326; hg19: chr2-75349046;