rs6715729

Variant names:

• chr2-75198602-A-G
• rs6715729
• NM_001058.4:c.333T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-75198602-A-G
• chr2-75198602-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001058.4(TACR1):​c.333T>C​(p.Phe111Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,613,960 control chromosomes in the GnomAD database, including 198,090 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 0.57 (27179 hom., cov: 33)
  • Exomes 𝑓: 0.48 (170911 hom.)
• Consequence: TACR1 NM_001058.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 27 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]

TACR1-AS1 (HGNC:58209):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.333T>C	p.Phe111Phe	synonymous_variant	Exon 1 of 5	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.333T>C	p.Phe111Phe	synonymous_variant	Exon 1 of 4		NP_056542.1
TACR1-AS1	NR_168009.1	n.372+42287A>G		intron_variant	Intron 2 of 3
TACR1-AS1	NR_168010.1	n.366+42287A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.333T>C	p.Phe111Phe	synonymous_variant	Exon 1 of 5	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.333T>C	p.Phe111Phe	synonymous_variant	Exon 1 of 4	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86736 AN: 152010 Hom.: 27143 Cov.: 33

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.476 AC: 119661 AN: 251454 AF XY: 0.465

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.407

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.478 AC: 699391 AN: 1461832 Hom.: 170911 Cov.: 58 AF XY: 0.474 AC XY: 344648 AN XY: 727214

African (AFR) AF: 0.868 AC: 29052 AN: 33480

American (AMR) AF: 0.462 AC: 20653 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9990 AN: 26136

East Asian (EAS) AF: 0.439 AC: 17418 AN: 39700

South Asian (SAS) AF: 0.396 AC: 34146 AN: 86256

European-Finnish (FIN) AF: 0.432 AC: 23087 AN: 53416

Middle Eastern (MID) AF: 0.475 AC: 2739 AN: 5766

European-Non Finnish (NFE) AF: 0.480 AC: 533325 AN: 1111958

Other (OTH) AF: 0.480 AC: 28981 AN: 60396

GnomAD4 genome AF: 0.571 AC: 86833 AN: 152128 Hom.: 27179 Cov.: 33 AF XY: 0.563 AC XY: 41870 AN XY: 74344

African (AFR) AF: 0.852 AC: 35390 AN: 41516

American (AMR) AF: 0.492 AC: 7535 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2085 AN: 5164

South Asian (SAS) AF: 0.406 AC: 1952 AN: 4804

European-Finnish (FIN) AF: 0.438 AC: 4630 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32385 AN: 67988

Other (OTH) AF: 0.540 AC: 1141 AN: 2114

Alfa AF: 0.516 Hom.: 13815

Bravo AF: 0.590

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		2.1
PromoterAI		0.0070	Neutral
Mutation Taster		=98/2	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: rs6715729; hg19: chr2-75425728; COSMIC: COSV59482069;