2-75050887-T-G

Variant names:

• chr2-75050887-T-G
• rs1106854
• NM_001058.4:c.932+364A>C

Variant summary

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

The NM_001058.4(TACR1):​c.932+364A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 306,672 control chromosomes in the GnomAD database, including 671 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 0.060 (491 hom., cov: 33)
  • Exomes 𝑓: 0.035 (180 hom.)
• Consequence: TACR1 NM_001058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.932+364A>C		intron_variant	Intron 4 of 4	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.*360A>C		downstream_gene_variant			NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.932+364A>C		intron_variant	Intron 4 of 4	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.*360A>C		downstream_gene_variant		1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9073 AN: 152110 Hom.: 493 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0603

GnomAD4 exome AF: 0.0353 AC: 5456 AN: 154444 Hom.: 180 AF XY: 0.0380 AC XY: 3107 AN XY: 81744

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.00288

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.0191

Gnomad4 NFE exome AF: 0.0232

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0597 AC: 9087 AN: 152228 Hom.: 491 Cov.: 33 AF XY: 0.0587 AC XY: 4373 AN XY: 74436

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00503

Gnomad4 SAS AF: 0.0798

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0200 Hom.: 1179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1106854; hg19: chr2-75278014;