rs3771829

Positions:

• chr2-75137019-C-G

Variant summary

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

The NM_001058.4(TACR1):​c.390-16251G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,164 control chromosomes in the GnomAD database, including 1,208 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 0.11 (1208 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACR1	NM_001058.4	c.390-16251G>C		intron_variant		ENST00000305249.10
TACR1	NM_015727.3	c.390-16251G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR1	ENST00000305249.10	c.390-16251G>C		intron_variant		1	NM_001058.4	P1
TACR1	ENST00000409848.3	c.390-16251G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16899 AN: 152046 Hom.: 1206 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.111 AC: 16909 AN: 152164 Hom.: 1208 Cov.: 32 AF XY: 0.114 AC XY: 8505 AN XY: 74400

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.122

Alfa AF: 0.101 Hom.: 123

Bravo AF: 0.124

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.53

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: rs3771829; hg19: chr2-75364145;