5-32711527-C-A

Variant names:

• chr5-32711527-C-A
• rs9716700
• NM_001204375.2:c.-250C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204375.2(NPR3):​c.-250C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,199,638 control chromosomes in the GnomAD database, including 20,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1745 hom., cov: 30)
  • Exomes 𝑓: 0.18 (18463 hom.)
• Consequence: NPR3 NM_001204375.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.685
• Publications: 9 publications found

Genes affected

NPR3 (HGNC:7945): (natriuretic peptide receptor 3) This gene encodes one of three natriuretic peptide receptors. Natriutetic peptides are small peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function as well as some metabolic and growth processes. The product of this gene encodes a natriuretic peptide receptor responsible for clearing circulating and extracellular natriuretic peptides through endocytosis of the receptor. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

NPR3 Gene-Disease associations (from GenCC):

• Boudin-Mortier syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-32711527-C-A is Benign according to our data. Variant chr5-32711527-C-A is described in ClinVar as Benign. ClinVar VariationId is 1177755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.-250C>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.-250C>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20022 AN: 149838 Hom.: 1745 Cov.: 30

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000987

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.181 AC: 190449 AN: 1049700 Hom.: 18463 Cov.: 20 AF XY: 0.181 AC XY: 89675 AN XY: 494978

African (AFR) AF: 0.0249 AC: 554 AN: 22250

American (AMR) AF: 0.144 AC: 1188 AN: 8242

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 1688 AN: 13640

East Asian (EAS) AF: 0.000869 AC: 21 AN: 24172

South Asian (SAS) AF: 0.0813 AC: 1529 AN: 18808

European-Finnish (FIN) AF: 0.162 AC: 2802 AN: 17316

Middle Eastern (MID) AF: 0.133 AC: 373 AN: 2810

European-Non Finnish (NFE) AF: 0.195 AC: 175724 AN: 900064

Other (OTH) AF: 0.155 AC: 6570 AN: 42398

GnomAD4 genome AF: 0.133 AC: 20009 AN: 149938 Hom.: 1745 Cov.: 30 AF XY: 0.131 AC XY: 9564 AN XY: 73074

African (AFR) AF: 0.0360 AC: 1458 AN: 40534

American (AMR) AF: 0.158 AC: 2376 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 435 AN: 3466

East Asian (EAS) AF: 0.000989 AC: 5 AN: 5054

South Asian (SAS) AF: 0.0738 AC: 346 AN: 4686

European-Finnish (FIN) AF: 0.181 AC: 1834 AN: 10134

Middle Eastern (MID) AF: 0.100 AC: 29 AN: 290

European-Non Finnish (NFE) AF: 0.190 AC: 12857 AN: 67758

Other (OTH) AF: 0.145 AC: 302 AN: 2078

Alfa AF: 0.153 Hom.: 294

Bravo AF: 0.127

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10489108) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		0.69
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9716700; hg19: chr5-32711633;