rs10082235

Positions:

• chr1-153684174-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000906.4(NPR1):​c.1484+350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,920 control chromosomes in the GnomAD database, including 4,165 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 0.17 (4165 hom., cov: 31)
• Consequence: NPR1 NM_000906.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00

Genes affected

NPR1 (HGNC:7943): (natriuretic peptide receptor 1) Guanylyl cyclases, catalyzing the production of cGMP from GTP, are classified as soluble and membrane forms (Garbers and Lowe, 1994 [PubMed 7982997]). The membrane guanylyl cyclases, often termed guanylyl cyclases A through F, form a family of cell-surface receptors with a similar topographic structure: an extracellular ligand-binding domain, a single membrane-spanning domain, and an intracellular region that contains a protein kinase-like domain and a cyclase catalytic domain. GC-A and GC-B function as receptors for natriuretic peptides; they are also referred to as atrial natriuretic peptide receptor A (NPR1) and type B (NPR2; MIM 108961). Also see NPR3 (MIM 108962), which encodes a protein with only the ligand-binding transmembrane and 37-amino acid cytoplasmic domains. NPR1 is a membrane-bound guanylate cyclase that serves as the receptor for both atrial and brain natriuretic peptides (ANP (MIM 108780) and BNP (MIM 600295), respectively).[supplied by OMIM, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR1	NM_000906.4	c.1484+350C>T		intron_variant		ENST00000368680.4
NPR1	XM_005245218.3	c.1484+350C>T		intron_variant
NPR1	XM_017001374.3	c.1484+350C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR1	ENST00000368680.4	c.1484+350C>T		intron_variant		1	NM_000906.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26346 AN: 151802 Hom.: 4137 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.174 AC: 26414 AN: 151920 Hom.: 4165 Cov.: 31 AF XY: 0.171 AC XY: 12670 AN XY: 74250

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0997 Hom.: 1213

Bravo AF: 0.188

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.073
DANN	Benign	0.19

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

LitVar

Other links and lift over

dbSNP: rs10082235; hg19: chr1-153656650;