chr2-75139811-C-T

Variant names:

• chr2-75139811-C-T
• rs3771833
• NM_001058.4:c.390-19043G>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.390-19043G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,060 control chromosomes in the GnomAD database, including 1,644 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 0.14 (1644 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641
• Publications: 13 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.390-19043G>A		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.390-19043G>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.390-19043G>A		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.390-19043G>A		intron_variant	Intron 1 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21359 AN: 151942 Hom.: 1646 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.141 AC: 21375 AN: 152060 Hom.: 1644 Cov.: 32 AF XY: 0.142 AC XY: 10561 AN XY: 74322

African (AFR) AF: 0.150 AC: 6231 AN: 41472

American (AMR) AF: 0.215 AC: 3279 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1060 AN: 5176

South Asian (SAS) AF: 0.151 AC: 731 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1116 AN: 10558

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7667 AN: 67978

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.129 Hom.: 5842

Bravo AF: 0.154

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		0.64
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: rs3771833; hg19: chr2-75366937;