2-75053080-T-C

Variant names:

• chr2-75053080-T-C
• rs727156
• NM_001058.4:c.735+525A>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.735+525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,906 control chromosomes in the GnomAD database, including 3,948 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 0.21 (3948 hom., cov: 31)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.735+525A>G		intron_variant	Intron 3 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.735+525A>G		intron_variant	Intron 3 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.735+525A>G		intron_variant	Intron 3 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.735+525A>G		intron_variant	Intron 3 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32015 AN: 151788 Hom.: 3930 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.211 AC: 32075 AN: 151906 Hom.: 3948 Cov.: 31 AF XY: 0.210 AC XY: 15601 AN XY: 74244

African (AFR) AF: 0.321 AC: 13283 AN: 41392

American (AMR) AF: 0.242 AC: 3687 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1110 AN: 5138

South Asian (SAS) AF: 0.249 AC: 1191 AN: 4788

European-Finnish (FIN) AF: 0.115 AC: 1212 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10393 AN: 67964

Other (OTH) AF: 0.212 AC: 447 AN: 2106

Alfa AF: 0.182 Hom.: 381

Bravo AF: 0.225

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.39
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: rs727156; hg19: chr2-75280207;