2-75124822-A-G

Variant names:

• chr2-75124822-A-G
• rs3771823
• NM_001058.4:c.390-4054T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001058.4(TACR1):​c.390-4054T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,076 control chromosomes in the GnomAD database, including 18,448 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 0.48 (18448 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.390-4054T>C		intron_variant	Intron 1 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.390-4054T>C		intron_variant	Intron 1 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.390-4054T>C		intron_variant	Intron 1 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.390-4054T>C		intron_variant	Intron 1 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73203 AN: 151958 Hom.: 18447 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.482 AC: 73229 AN: 152076 Hom.: 18448 Cov.: 32 AF XY: 0.473 AC XY: 35150 AN XY: 74326

African (AFR) AF: 0.476 AC: 19721 AN: 41474

American (AMR) AF: 0.398 AC: 6073 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3470

East Asian (EAS) AF: 0.110 AC: 572 AN: 5180

South Asian (SAS) AF: 0.321 AC: 1551 AN: 4826

European-Finnish (FIN) AF: 0.507 AC: 5344 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36710 AN: 67998

Other (OTH) AF: 0.461 AC: 973 AN: 2112

Alfa AF: 0.509 Hom.: 58006

Bravo AF: 0.471

Asia WGS AF: 0.237 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		1.6
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: rs3771823; hg19: chr2-75351948;