rs3891075

Variant names:

• chr1-153685711-A-T
• rs3891075
• NM_000906.4:c.1606-95A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000906.4(NPR1):​c.1606-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 922,988 control chromosomes in the GnomAD database, including 4,217 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 0.11 (1284 hom., cov: 31)
  • Exomes 𝑓: 0.076 (2933 hom.)
• Consequence: NPR1 NM_000906.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000906.4. 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
	NPR1	NM_000906.4	MANE Select	c.1606-95A>T		intron	N/A	NP_000897.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR1	ENST00000368680.4	TSL:1 MANE Select	c.1606-95A>T		intron	N/A	ENSP00000357669.3	P16066
	NPR1	ENST00000955927.1		c.1606-95A>T		intron	N/A	ENSP00000625986.1
	NPR1	ENST00000932961.1		c.1606-95A>T		intron	N/A	ENSP00000603020.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16794 AN: 151950 Hom.: 1270 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0765 AC: 58969 AN: 770922 Hom.: 2933 AF XY: 0.0774 AC XY: 31470 AN XY: 406610

African (AFR) AF: 0.231 AC: 4398 AN: 19026

American (AMR) AF: 0.0590 AC: 1991 AN: 33770

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2411 AN: 19708

East Asian (EAS) AF: 0.000165 AC: 6 AN: 36444

South Asian (SAS) AF: 0.0972 AC: 6410 AN: 65930

European-Finnish (FIN) AF: 0.0606 AC: 3118 AN: 51492

Middle Eastern (MID) AF: 0.206 AC: 891 AN: 4326

European-Non Finnish (NFE) AF: 0.0724 AC: 36396 AN: 502744

Other (OTH) AF: 0.0893 AC: 3348 AN: 37482

GnomAD4 genome AF: 0.111 AC: 16834 AN: 152066 Hom.: 1284 Cov.: 31 AF XY: 0.109 AC XY: 8103 AN XY: 74350

African (AFR) AF: 0.217 AC: 8978 AN: 41422

American (AMR) AF: 0.0794 AC: 1213 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4816

European-Finnish (FIN) AF: 0.0633 AC: 670 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4794 AN: 67994

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.0935 Hom.: 118

Bravo AF: 0.117

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.028
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: rs3891075; hg19: chr1-153658187;