5-32774941-G-T

Variant names:

• chr5-32774941-G-T
• rs1173743
• NM_001204375.2:c.1195+98G>T

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.1195+98G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 907,852 control chromosomes in the GnomAD database, including 137,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27615 hom., cov: 32)
  • Exomes 𝑓: 0.53 (110112 hom.)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 10 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=-0.9).
• BP6: Variant 5-32774941-G-T is Benign according to our data. Variant chr5-32774941-G-T is described in ClinVar as Benign. ClinVar VariationId is 1222046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204375.2. 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
	NPR3	NM_001204375.2	MANE Select	c.1195+98G>T		intron	N/A	NP_001191304.1	P17342-1
	NPR3	NM_000908.4		c.1195+98G>T		intron	N/A	NP_000899.1	P17342-2
	NPR3	NM_001363652.2		c.547+98G>T		intron	N/A	NP_001350581.1	C9JK69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.1195+98G>T		intron	N/A	ENSP00000265074.8	P17342-1
	NPR3	ENST00000415167.2	TSL:1	c.1195+98G>T		intron	N/A	ENSP00000398028.2	P17342-2
	NPR3	ENST00000506712.1	TSL:1	n.556+98G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90166 AN: 151926 Hom.: 27565 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.534 AC: 403498 AN: 755808 Hom.: 110112 AF XY: 0.537 AC XY: 213308 AN XY: 397422

African (AFR) AF: 0.737 AC: 14340 AN: 19466

American (AMR) AF: 0.487 AC: 19736 AN: 40506

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 10895 AN: 19796

East Asian (EAS) AF: 0.598 AC: 21639 AN: 36188

South Asian (SAS) AF: 0.592 AC: 38918 AN: 65696

European-Finnish (FIN) AF: 0.545 AC: 25169 AN: 46198

Middle Eastern (MID) AF: 0.551 AC: 2377 AN: 4316

European-Non Finnish (NFE) AF: 0.514 AC: 250291 AN: 486652

Other (OTH) AF: 0.544 AC: 20133 AN: 36990

GnomAD4 genome AF: 0.594 AC: 90279 AN: 152044 Hom.: 27615 Cov.: 32 AF XY: 0.596 AC XY: 44298 AN XY: 74314

African (AFR) AF: 0.738 AC: 30626 AN: 41506

American (AMR) AF: 0.550 AC: 8397 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3262 AN: 5164

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5796 AN: 10550

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35534 AN: 67948

Other (OTH) AF: 0.582 AC: 1227 AN: 2110

Alfa AF: 0.550 Hom.: 42185

Bravo AF: 0.598

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.73
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1173743; hg19: chr5-32775047; COSMIC: COSV54089243;