chr1-11857283-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPB	NM_002521.3	c.*372G>A		downstream_gene_variant		ENST00000376468.4	NP_002512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPPB	ENST00000376468.4	c.*372G>A		downstream_gene_variant		1	NM_002521.3	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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.451

Alfa AF: 0.433 Hom.: 19264

Bravo AF: 0.464

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs198388; hg19: chr1-11917340;