rs12612207

Positions:

• chr2-11667090-C-T

Variant summary

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

The NM_012344.4(NTSR2):​c.624+2416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,142 control chromosomes in the GnomAD database, including 15,887 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 0.43 (15887 hom., cov: 33)
• Consequence: NTSR2 NM_012344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

NTSR2 (HGNC:8040): (neurotensin receptor 2) The protein encoded by this gene belongs to the G protein-coupled receptor family that activate a phosphatidylinositol-calcium second messenger system. Binding and pharmacological studies demonstrate that this receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. However, unlike NT1 receptor, this gene recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with neurotensin for low-affinity binding sites in brain. These activities suggest that this receptor may be of physiological importance and that a natural agonist for the receptor may exist. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTSR2	NM_012344.4	c.624+2416G>A		intron_variant		ENST00000306928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTSR2	ENST00000306928.6	c.624+2416G>A		intron_variant		1	NM_012344.4	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65523 AN: 152024 Hom.: 15897 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.431 AC: 65511 AN: 152142 Hom.: 15887 Cov.: 33 AF XY: 0.434 AC XY: 32261 AN XY: 74384

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.457

Alfa AF: 0.492 Hom.: 9973

Bravo AF: 0.418

Asia WGS AF: 0.496 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.8
DANN	Benign	0.76

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: rs12612207; hg19: chr2-11807216;