dbSNP rs5268: NPPC:c.*20+62G>A (chr2-231925343-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024409.4(NPPC):c.*20+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,357,522 control chromosomes in the GnomAD database, including 252,140 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 0.55 ( 23654 hom., cov: 34)

Exomes 𝑓: 0.61 ( 228486 hom. )

Consequence

NPPC
NM_024409.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.163

Publications

14 publications found

Variant links:

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

NPPC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPC	NM_024409.4	MANE Select	c.*20+62G>A		intron	N/A	NP_077720.1	P23582

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPPC	ENST00000409852.2	TSL:3 MANE Select	c.*20+62G>A	intron	N/A	ENSP00000387159.1	P23582
NPPC	ENST00000968048.1		c.*20+62G>A	intron	N/A	ENSP00000638107.1
NPPC	ENST00000968049.1		c.*20+62G>A	intron	N/A	ENSP00000638108.1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83170

AN:

152014

Hom.:

23650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.542

GnomAD4 exome

AF:

0.609

AC:

733828

AN:

1205394

Hom.:

228486

Cov.:

AF XY:

0.606

AC XY:

354477

AN XY:

584532

show subpopulations

African (AFR)

AF:

0.481

AC:

11472

AN:

23872

American (AMR)

AF:

0.427

AC:

4476

AN:

10486

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

9592

AN:

16746

East Asian (EAS)

AF:

0.159

AC:

4527

AN:

28392

South Asian (SAS)

AF:

0.491

AC:

26522

AN:

54028

European-Finnish (FIN)

AF:

0.617

AC:

23527

AN:

38122

Middle Eastern (MID)

AF:

0.529

AC:

1971

AN:

3726

European-Non Finnish (NFE)

AF:

0.635

AC:

622919

AN:

980378

Other (OTH)

AF:

0.581

AC:

28822

AN:

49644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

13604

27207

40811

54414

68018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17248

34496

51744

68992

86240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

83201

AN:

152128

Hom.:

23654

Cov.:

AF XY:

0.541

AC XY:

40227

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.490

AC:

20349

AN:

41508

American (AMR)

AF:

0.438

AC:

6704

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1981

AN:

3472

East Asian (EAS)

AF:

0.198

AC:

1023

AN:

5164

South Asian (SAS)

AF:

0.450

AC:

2174

AN:

4832

European-Finnish (FIN)

AF:

0.622

AC:

6583

AN:

10580

Middle Eastern (MID)

AF:

0.575

AC:

168

AN:

292

European-Non Finnish (NFE)

AF:

0.628

AC:

42692

AN:

67964

Other (OTH)

AF:

0.541

AC:

1144

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1902

3804

5707

7609

9511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.595

Hom.:

3431

Bravo

AF:

0.525

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over