rs1800832

Positions:

• chr12-85874401-A-G
• chr12-85874401-A-T

Variant summary

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

The NM_006183.5(NTS):​c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 1,609,968 control chromosomes in the GnomAD database, including 8,342 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 0.076 (605 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7737 hom.)
• Consequence: NTS NM_006183.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

NTS (HGNC:8038): (neurotensin) This gene encodes a common precursor for two peptides, neuromedin N and neurotensin. Neurotensin is a secreted tridecapeptide, which is widely distributed throughout the central nervous system, and may function as a neurotransmitter or a neuromodulator. It may be involved in dopamine-associated pathophysiological events, in the maintenance of gut structure and function, and in the regulation of fat metabolism. Neurotensin also exhibits antimicrobial activity against bacteria and fungi. Tissue-specific processing may lead to the formation in some tissues of larger forms of neuromedin N and neurotensin. The large forms may represent more stable peptides that are also biologically active. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTS	NM_006183.5	c.-3A>G		5_prime_UTR_variant	1/4	ENST00000256010.7	NP_006174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTS	ENST00000256010	c.-3A>G		5_prime_UTR_variant	1/4	1	NM_006183.5	ENSP00000256010.5
NTS	ENST00000551529	c.-3A>G		5_prime_UTR_variant	1/3	3		ENSP00000448328.1

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11566 AN: 152098 Hom.: 606 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0937

GnomAD3 exomes AF: 0.0815 AC: 20486 AN: 251238 Hom.: 1163 AF XY: 0.0846 AC XY: 11488 AN XY: 135784

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.0553

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0554

Gnomad FIN exome AF: 0.0781

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0968 AC: 141109 AN: 1457752 Hom.: 7737 Cov.: 29 AF XY: 0.0966 AC XY: 70111 AN XY: 725526

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0576

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0577

Gnomad4 FIN exome AF: 0.0806

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0998

GnomAD4 genome AF: 0.0760 AC: 11562 AN: 152216 Hom.: 605 Cov.: 32 AF XY: 0.0740 AC XY: 5510 AN XY: 74410

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0927

Alfa AF: 0.103 Hom.: 487

Bravo AF: 0.0752

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.80

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: rs1800832; hg19: chr12-86268179;