rs198389

Variant names:

• chr1-11859214-A-G
• rs198389
• ENST00000945854.1:c.-381T>C

Variant summary

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

The ENST00000945854.1(NPPB):​c.-381T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,080 control chromosomes in the GnomAD database, including 12,025 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 0.39 (12025 hom., cov: 32)
• Consequence: NPPB ENST00000945854.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51
• Publications: 100 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000945854.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPB	ENST00000945854.1		c.-381T>C		upstream_gene	N/A	ENSP00000615913.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59573 AN: 151962 Hom.: 12003 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.392 AC: 59635 AN: 152080 Hom.: 12025 Cov.: 32 AF XY: 0.390 AC XY: 28982 AN XY: 74362

African (AFR) AF: 0.408 AC: 16936 AN: 41492

American (AMR) AF: 0.284 AC: 4346 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3464

East Asian (EAS) AF: 0.179 AC: 927 AN: 5174

South Asian (SAS) AF: 0.490 AC: 2368 AN: 4828

European-Finnish (FIN) AF: 0.369 AC: 3909 AN: 10582

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28488 AN: 67946

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.409 Hom.: 50171

Bravo AF: 0.383

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.090
DANN	Benign	0.28
PhyloP100		-3.5
PromoterAI		0.37	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs198389;

hg19: chr1-11919271;

COSMIC: COSV64687424;