2-75097459-T-A

Variant names:

• chr2-75097459-T-A
• rs4853105
• NM_001058.4:c.584+23115A>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.584+23115A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,894 control chromosomes in the GnomAD database, including 38,000 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 0.70 (38000 hom., cov: 30)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	NM_001058.4	MANE Select	c.584+23115A>T		intron	N/A	NP_001049.1
	TACR1	NM_015727.3		c.584+23115A>T		intron	N/A	NP_056542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	ENST00000305249.10	TSL:1 MANE Select	c.584+23115A>T		intron	N/A	ENSP00000303522.4
	TACR1	ENST00000409848.3	TSL:1	c.584+23115A>T		intron	N/A	ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106762 AN: 151776 Hom.: 37955 Cov.: 30

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.704 AC: 106863 AN: 151894 Hom.: 38000 Cov.: 30 AF XY: 0.700 AC XY: 51918 AN XY: 74220

African (AFR) AF: 0.799 AC: 33098 AN: 41424

American (AMR) AF: 0.684 AC: 10430 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2505 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3457 AN: 5162

South Asian (SAS) AF: 0.585 AC: 2816 AN: 4816

European-Finnish (FIN) AF: 0.647 AC: 6803 AN: 10518

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45444 AN: 67932

Other (OTH) AF: 0.694 AC: 1466 AN: 2112

Alfa AF: 0.564 Hom.: 1507

Bravo AF: 0.714

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		-0.064
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: rs4853105; hg19: chr2-75324586;