rs735668

chr2-75135918-A-Cchr2-75135918-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.390-15150T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,908 control chromosomes in the GnomAD database, including 14,007 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 0.41 (14007 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACR1	NM_001058.4	c.390-15150T>G		intron_variant		ENST00000305249.10
TACR1	NM_015727.3	c.390-15150T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR1	ENST00000305249.10	c.390-15150T>G		intron_variant		1	NM_001058.4	P1
TACR1	ENST00000409848.3	c.390-15150T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62881 AN: 151790 Hom.: 14007 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.414 AC: 62892 AN: 151908 Hom.: 14007 Cov.: 32 AF XY: 0.409 AC XY: 30325 AN XY: 74232

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.405

Alfa AF: 0.475 Hom.: 16362

Bravo AF: 0.398

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.64

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: rs735668; hg19: chr2-75363044;