2-75118069-T-G

Variant names:

• chr2-75118069-T-G
• rs6741029
• NM_001058.4:c.584+2505A>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.584+2505A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,992 control chromosomes in the GnomAD database, including 33,009 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 0.66 (33009 hom., cov: 32)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 11 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.584+2505A>C		intron_variant	Intron 2 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.584+2505A>C		intron_variant	Intron 2 of 3		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.584+2505A>C		intron_variant	Intron 2 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.584+2505A>C		intron_variant	Intron 2 of 3	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99838 AN: 151874 Hom.: 33002 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.657 AC: 99878 AN: 151992 Hom.: 33009 Cov.: 32 AF XY: 0.653 AC XY: 48558 AN XY: 74318

African (AFR) AF: 0.698 AC: 28928 AN: 41430

American (AMR) AF: 0.656 AC: 10024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2455 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2993 AN: 5170

South Asian (SAS) AF: 0.584 AC: 2823 AN: 4830

European-Finnish (FIN) AF: 0.601 AC: 6352 AN: 10566

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44188 AN: 67924

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.652 Hom.: 145271

Bravo AF: 0.665

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.71
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: rs6741029; hg19: chr2-75345195;