rs13385681

Variant names:

• chr2-100470432-G-A
• rs13385681
• NM_001011717.1:c.-57G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-100470432-G-A
• chr2-100470432-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001011717.1(NMS):​c.-57G>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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011717.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMS	NM_001011717.1	MANE Select	c.-57G>A		upstream_gene	N/A	NP_001011717.1	A0A250SI41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMS	ENST00000376865.1	TSL:1 MANE Select	c.-57G>A		upstream_gene	N/A	ENSP00000366061.1	Q5H8A3

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

African (AFR) AF: 0.257 AC: 7429 AN: 28854

American (AMR) AF: 0.195 AC: 8674 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4155 AN: 24722

East Asian (EAS) AF: 0.320 AC: 12283 AN: 38410

South Asian (SAS) AF: 0.279 AC: 22750 AN: 81624

European-Finnish (FIN) AF: 0.219 AC: 11490 AN: 52480

Middle Eastern (MID) AF: 0.165 AC: 883 AN: 5352

European-Non Finnish (NFE) AF: 0.209 AC: 189920 AN: 908392

Other (OTH) AF: 0.211 AC: 11136 AN: 52730

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

African (AFR) AF: 0.269 AC: 11141 AN: 41456

American (AMR) AF: 0.193 AC: 2952 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1788 AN: 5158

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4818

European-Finnish (FIN) AF: 0.229 AC: 2423 AN: 10568

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14840 AN: 67948

Other (OTH) AF: 0.204 AC: 429 AN: 2108

Alfa AF: 0.218 Hom.: 4716

Bravo AF: 0.234

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		-0.41
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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