rs2024512

Variant names:

• chr2-75198497-G-A
• rs2024512
• NM_001058.4:c.389+49C>T

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+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,588,712 control chromosomes in the GnomAD database, including 182,176 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 0.55 (24515 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157661 hom.)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 7 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]

TACR1-AS1 (HGNC:58209):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.389+49C>T		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.389+49C>T		intron_variant	Intron 1 of 3		NP_056542.1
TACR1-AS1	NR_168009.1	n.372+42182G>A		intron_variant	Intron 2 of 3
TACR1-AS1	NR_168010.1	n.366+42182G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.389+49C>T		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.389+49C>T		intron_variant	Intron 1 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82913 AN: 151902 Hom.: 24483 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.464 AC: 112243 AN: 241948 AF XY: 0.454

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.406

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.464 AC: 667216 AN: 1436692 Hom.: 157661 Cov.: 32 AF XY: 0.460 AC XY: 327089 AN XY: 710410

African (AFR) AF: 0.807 AC: 26622 AN: 32992

American (AMR) AF: 0.446 AC: 19590 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9648 AN: 25300

East Asian (EAS) AF: 0.437 AC: 17138 AN: 39200

South Asian (SAS) AF: 0.389 AC: 32569 AN: 83770

European-Finnish (FIN) AF: 0.428 AC: 22419 AN: 52430

Middle Eastern (MID) AF: 0.472 AC: 2367 AN: 5012

European-Non Finnish (NFE) AF: 0.465 AC: 509361 AN: 1094878

Other (OTH) AF: 0.464 AC: 27502 AN: 59212

GnomAD4 genome AF: 0.546 AC: 83003 AN: 152020 Hom.: 24515 Cov.: 32 AF XY: 0.540 AC XY: 40100 AN XY: 74278

African (AFR) AF: 0.795 AC: 32970 AN: 41474

American (AMR) AF: 0.470 AC: 7189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2080 AN: 5146

South Asian (SAS) AF: 0.398 AC: 1912 AN: 4810

European-Finnish (FIN) AF: 0.432 AC: 4551 AN: 10538

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31493 AN: 67974

Other (OTH) AF: 0.518 AC: 1094 AN: 2114

Alfa AF: 0.523 Hom.: 5385

Bravo AF: 0.563

Asia WGS AF: 0.441 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.54
PhyloP100		-0.19
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: rs2024512; hg19: chr2-75425623; COSMIC: COSV59478877;