rs3107179

Variant names:

• chr2-231923615-C-T
• rs3107179
• NM_024409.4:c.*21-1300G>A

Variant summary

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

The NM_024409.4(NPPC):​c.*21-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,042 control chromosomes in the GnomAD database, including 18,042 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 0.45 (18042 hom., cov: 32)
• Consequence: NPPC NM_024409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.07
• Publications: 7 publications found

Genes affected

NPPC (HGNC:7941): (natriuretic peptide C) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cardiac natriuretic peptides CNP-53, CNP-29 and CNP-22, which belong to the natriuretic family of peptides. The encoded peptides exhibit vasorelaxation activity in laboratory animals and elevated levels of CNP-22 have been observed in the plasma of chronic heart failure patients. [provided by RefSeq, Oct 2015]

NPPC Gene-Disease associations (from GenCC):

• short stature with nonspecific skeletal abnormalities 1

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPC	NM_024409.4	MANE Select	c.*21-1300G>A		intron	N/A	NP_077720.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPC	ENST00000409852.2	TSL:3 MANE Select	c.*21-1300G>A		intron	N/A	ENSP00000387159.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68581 AN: 151924 Hom.: 18042 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.451 AC: 68594 AN: 152042 Hom.: 18042 Cov.: 32 AF XY: 0.447 AC XY: 33267 AN XY: 74344

African (AFR) AF: 0.204 AC: 8445 AN: 41490

American (AMR) AF: 0.390 AC: 5948 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1914 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1027 AN: 5174

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4808

European-Finnish (FIN) AF: 0.585 AC: 6182 AN: 10566

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41348 AN: 67948

Other (OTH) AF: 0.471 AC: 995 AN: 2114

Alfa AF: 0.546 Hom.: 72310

Bravo AF: 0.421

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.025
DANN	Benign	0.77
PhyloP100		-5.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3107179; hg19: chr2-232788325; COSMIC: COSV54945208; COSMIC: COSV54945208;