1-11857283-C-T

Variant names:

• chr1-11857283-C-T
• rs198388
• NM_002521.3:c.*372G>A

Variant summary

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

The NM_002521.3(NPPB):​c.*372G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,924 control chromosomes in the GnomAD database, including 17,535 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 0.46 (17535 hom., cov: 31)
• Consequence: NPPB NM_002521.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 34 publications found

Genes affected

NPPB (HGNC:7940): (natriuretic peptide B) This gene is a member of the natriuretic peptide family and encodes a secreted protein which functions as a cardiac hormone. The protein undergoes two cleavage events, one within the cell and a second after secretion into the blood. The protein's biological actions include natriuresis, diuresis, vasorelaxation, inhibition of renin and aldosterone secretion, and a key role in cardiovascular homeostasis. A high concentration of this protein in the bloodstream is indicative of heart failure. The presence of myocardial injury is a significant predictor of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients, and there is evidence of increased levels of natriuretic peptide B in hospitalized non-survivor COVID-19 patients. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Mutations in this gene have been associated with postmenopausal osteoporosis. [provided by RefSeq, Aug 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002521.3. 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
	NPPB	NM_002521.3	MANE Select	c.*372G>A		downstream_gene	N/A	NP_002512.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPB	ENST00000376468.4	TSL:1 MANE Select	c.*372G>A		downstream_gene	N/A	ENSP00000365651.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70556 AN: 151806 Hom.: 17501 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.465 AC: 70640 AN: 151924 Hom.: 17535 Cov.: 31 AF XY: 0.459 AC XY: 34089 AN XY: 74234

African (AFR) AF: 0.631 AC: 26130 AN: 41428

American (AMR) AF: 0.315 AC: 4818 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3464

East Asian (EAS) AF: 0.190 AC: 981 AN: 5164

South Asian (SAS) AF: 0.529 AC: 2546 AN: 4810

European-Finnish (FIN) AF: 0.371 AC: 3906 AN: 10538

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29371 AN: 67942

Other (OTH) AF: 0.451 AC: 950 AN: 2108

Alfa AF: 0.437 Hom.: 24866

Bravo AF: 0.464

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs198388; hg19: chr1-11917340;