chr2-75198497-G-A

Position:

• chr2-75198497-G-A

Variant summary

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

The NM_001058.4(TACR1):​c.389+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,588,712 control chromosomes in the GnomAD database, including 182,176 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 0.55 (24515 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157661 hom.)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR1	NM_001058.4	c.389+49C>T		intron_variant		ENST00000305249.10	NP_001049.1
LOC105374811	NR_168009.1	n.372+42182G>A		intron_variant, non_coding_transcript_variant
TACR1	NM_015727.3	c.389+49C>T		intron_variant			NP_056542.1
LOC105374811	NR_168010.1	n.366+42182G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.389+49C>T		intron_variant		1	NM_001058.4	ENSP00000303522	P1
TACR1	ENST00000409848.3	c.389+49C>T		intron_variant		1		ENSP00000386448

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82913 AN: 151902 Hom.: 24483 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.464 AC: 112243 AN: 241948 Hom.: 27152 AF XY: 0.454 AC XY: 59312 AN XY: 130558

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.406

Gnomad SAS exome AF: 0.392

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.464 AC: 667216 AN: 1436692 Hom.: 157661 Cov.: 32 AF XY: 0.460 AC XY: 327089 AN XY: 710410

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.546 AC: 83003 AN: 152020 Hom.: 24515 Cov.: 32 AF XY: 0.540 AC XY: 40100 AN XY: 74278

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.518

Alfa AF: 0.518 Hom.: 5155

Bravo AF: 0.563

Asia WGS AF: 0.441 AC: 1530 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	0.99
DANN	Benign	0.54

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: rs2024512; hg19: chr2-75425623; COSMIC: COSV59478877;