rs13385681

chr2-100470432-G-Achr2-100470432-G-C

Variant summary

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

The 2-100470432-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,388,972 control chromosomes in the GnomAD database, including 34,381 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 0.24 (4441 hom., cov: 32)
  • Exomes 𝑓: 0.22 (29940 hom.)
• Consequence: NMS NM_001011717.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

Genes affected

NMS (HGNC:32203): (neuromedin S) This gene encodes a member of the neuromedin family of neuropeptides. The encoded preproprotein is proteolytically processed to generate a biologically active neuropeptide that plays a role in the regulation of circadian rhythm, anorexigenic action, antidiuretic action, cardiovascular function and stimulation of oxytocin and vasopressin release. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMS	NM_001011717.1			upstream_gene_variant		ENST00000376865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMS	ENST00000376865.1			upstream_gene_variant		1	NM_001011717.1	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35824 AN: 151882 Hom.: 4443 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.217 AC: 268720 AN: 1236972 Hom.: 29940 Cov.: 18 AF XY: 0.219 AC XY: 137612 AN XY: 627110

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.236 AC: 35833 AN: 152000 Hom.: 4441 Cov.: 32 AF XY: 0.237 AC XY: 17575 AN XY: 74302

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.204

Alfa AF: 0.216 Hom.: 3498

Bravo AF: 0.234

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13385681; hg19: chr2-101086894; COSMIC: COSV65259184;