1-11858387-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002521.3(NPPB):​c.215G>A​(p.Arg72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,598,676 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 35 hom. )

Consequence

NPPB
NM_002521.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.39
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0033937693).
BP6
Variant 1-11858387-C-T is Benign according to our data. Variant chr1-11858387-C-T is described in ClinVar as [Benign]. Clinvar id is 722224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPPBNM_002521.3 linkc.215G>A p.Arg72His missense_variant Exon 2 of 3 ENST00000376468.4 NP_002512.1 P16860

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPPBENST00000376468.4 linkc.215G>A p.Arg72His missense_variant Exon 2 of 3 1 NM_002521.3 ENSP00000365651.3 P16860

Frequencies

GnomAD3 genomes
AF:
0.00277
AC:
421
AN:
152148
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00713
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0311
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00364
AC:
862
AN:
236984
Hom.:
13
AF XY:
0.00358
AC XY:
458
AN XY:
128106
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00721
Gnomad SAS exome
AF:
0.000179
Gnomad FIN exome
AF:
0.0300
Gnomad NFE exome
AF:
0.000640
Gnomad OTH exome
AF:
0.00451
GnomAD4 exome
AF:
0.00160
AC:
2313
AN:
1446410
Hom.:
35
Cov.:
32
AF XY:
0.00155
AC XY:
1109
AN XY:
717710
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000934
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00948
Gnomad4 SAS exome
AF:
0.000202
Gnomad4 FIN exome
AF:
0.0315
Gnomad4 NFE exome
AF:
0.000159
Gnomad4 OTH exome
AF:
0.00116
GnomAD4 genome
AF:
0.00276
AC:
421
AN:
152266
Hom.:
4
Cov.:
32
AF XY:
0.00379
AC XY:
282
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00714
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0311
Gnomad4 NFE
AF:
0.000706
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000673
Hom.:
0
Bravo
AF:
0.000510
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00315
AC:
383
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 27, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.65
DANN
Benign
0.50
DEOGEN2
Benign
0.051
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.37
T
MetaRNN
Benign
0.0034
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.19
T
PROVEAN
Benign
0.45
N
REVEL
Benign
0.0080
Sift
Benign
0.18
T
Sift4G
Benign
0.14
T
Polyphen
0.0
B
Vest4
0.049
MVP
0.18
MPC
0.24
ClinPred
0.018
T
GERP RS
-2.8
Varity_R
0.020
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61761991; hg19: chr1-11918444; COSMIC: COSV64687360; API