chr2-75049302-C-G

Variant names:

• chr2-75049302-C-G
• rs881
• NM_001058.4:c.*130G>C

Variant summary

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

The NM_001058.4(TACR1):​c.*130G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,016,610 control chromosomes in the GnomAD database, including 18,187 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 0.19 (2779 hom., cov: 33)
  • Exomes 𝑓: 0.18 (15408 hom.)
• Consequence: TACR1 NM_001058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.*130G>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000305249.10	NP_001049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.*130G>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001058.4	ENSP00000303522.4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28274 AN: 152074 Hom.: 2780 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.182 AC: 157309 AN: 864418 Hom.: 15408 Cov.: 11 AF XY: 0.187 AC XY: 81281 AN XY: 434074

African (AFR) AF: 0.187 AC: 3849 AN: 20610

American (AMR) AF: 0.266 AC: 5840 AN: 21974

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 2931 AN: 16434

East Asian (EAS) AF: 0.184 AC: 6375 AN: 34670

South Asian (SAS) AF: 0.341 AC: 19028 AN: 55734

European-Finnish (FIN) AF: 0.127 AC: 4706 AN: 36984

Middle Eastern (MID) AF: 0.198 AC: 559 AN: 2830

European-Non Finnish (NFE) AF: 0.168 AC: 106717 AN: 635320

Other (OTH) AF: 0.183 AC: 7304 AN: 39862

GnomAD4 genome AF: 0.186 AC: 28289 AN: 152192 Hom.: 2779 Cov.: 33 AF XY: 0.187 AC XY: 13944 AN XY: 74408

African (AFR) AF: 0.190 AC: 7894 AN: 41520

American (AMR) AF: 0.246 AC: 3757 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.168 AC: 871 AN: 5170

South Asian (SAS) AF: 0.337 AC: 1628 AN: 4828

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10602

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11563 AN: 67990

Other (OTH) AF: 0.213 AC: 451 AN: 2114

Alfa AF: 0.182 Hom.: 350

Bravo AF: 0.191

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs881; hg19: chr2-75276429; COSMIC: COSV59480908; COSMIC: COSV59480908;