2-75174939-A-G

Position:

• chr2-75174939-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001058.4(TACR1):​c.389+23607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,960 control chromosomes in the GnomAD database, including 26,119 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 0.58 (26119 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACR1	NM_001058.4	c.389+23607T>C		intron_variant		ENST00000305249.10
LOC105374811	NR_168009.1	n.372+18624A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR1	ENST00000305249.10	c.389+23607T>C		intron_variant		1	NM_001058.4	P1
TACR1	ENST00000409848.3	c.389+23607T>C		intron_variant		1
	ENST00000604271.2	n.319-11891A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88161 AN: 151842 Hom.: 26087 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.581 AC: 88254 AN: 151960 Hom.: 26119 Cov.: 32 AF XY: 0.582 AC XY: 43203 AN XY: 74242

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.564

Alfa AF: 0.571 Hom.: 44530

Bravo AF: 0.571

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs12477554; hg19: chr2-75402065;