rs4853105

Positions:

• chr2-75097459-T-A
• chr2-75097459-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.584+23115A>T		intron_variant		ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.584+23115A>T		intron_variant			NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.584+23115A>T		intron_variant		1	NM_001058.4	ENSP00000303522	P1
TACR1	ENST00000409848.3	c.584+23115A>T		intron_variant		1		ENSP00000386448

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

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.694

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.8
DANN	Benign	0.69

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: rs4853105; hg19: chr2-75324586;