rs975664

Positions:

• chr2-75141671-C-T

Variant summary

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

The NM_001058.4(TACR1):​c.390-20903G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,114 control chromosomes in the GnomAD database, including 20,247 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 0.50 (20247 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.390-20903G>A		intron_variant		ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.390-20903G>A		intron_variant			NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.390-20903G>A		intron_variant		1	NM_001058.4	ENSP00000303522	P1
TACR1	ENST00000409848.3	c.390-20903G>A		intron_variant		1		ENSP00000386448

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76039 AN: 151996 Hom.: 20235 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.500 AC: 76090 AN: 152114 Hom.: 20247 Cov.: 32 AF XY: 0.489 AC XY: 36388 AN XY: 74372

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.465

Alfa AF: 0.508 Hom.: 22534

Bravo AF: 0.498

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.47

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: rs975664; hg19: chr2-75368797;