rs3755457

Variant names:

• chr2-75064383-G-A
• rs3755457
• NM_001058.4:c.585-10628C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-75064383-G-A
• chr2-75064383-G-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.585-10628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,098 control chromosomes in the GnomAD database, including 7,969 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 0.28 (7969 hom., cov: 33)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.585-10628C>T		intron_variant	Intron 2 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.585-10628C>T		intron_variant	Intron 2 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.585-10628C>T		intron_variant	Intron 2 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.585-10628C>T		intron_variant	Intron 2 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42784 AN: 151980 Hom.: 7939 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.282 AC: 42876 AN: 152098 Hom.: 7969 Cov.: 33 AF XY: 0.283 AC XY: 21046 AN XY: 74358

African (AFR) AF: 0.501 AC: 20797 AN: 41478

American (AMR) AF: 0.362 AC: 5536 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1600 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4808

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10605 AN: 67980

Other (OTH) AF: 0.263 AC: 556 AN: 2114

Alfa AF: 0.210 Hom.: 5860

Bravo AF: 0.310

Asia WGS AF: 0.344 AC: 1197 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	3.5
DANN	Benign	0.72
PhyloP100		0.44
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: rs3755457; hg19: chr2-75291510;