rs6715729

chr2-75198602-A-Gchr2-75198602-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001058.4(TACR1):c.333T>C(p.Phe111=) 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

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]

LOC105374811 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TACR1	NM_001058.4	c.333T>C	p.Phe111=	synonymous_variant	1/5	ENST00000305249.10
LOC105374811	NR_168009.1	n.372+42287A>G		intron_variant, non_coding_transcript_variant
TACR1	NM_015727.3	c.333T>C	p.Phe111=	synonymous_variant	1/4
LOC105374811	NR_168010.1	n.366+42287A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR1	ENST00000305249.10	c.333T>C	p.Phe111=	synonymous_variant	1/5	1	NM_001058.4	P1
TACR1	ENST00000409848.3	c.333T>C	p.Phe111=	synonymous_variant	1/4	1

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

GnomAD3 exomes AF: 0.476 AC: 119661 AN: 251454 Hom.: 29933 AF XY: 0.465 AC XY: 63205 AN XY: 135896

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 SAS exome AF: 0.400

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

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.480

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

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.540

Alfa AF: 0.515 Hom.: 10150

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

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: rs6715729; hg19: chr2-75425728; COSMIC: COSV59482069;