rs164147

Positions:

• chr1-162368607-A-C
• chr1-162368607-A-G

Variant summary

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

The NM_014697.3(NOS1AP):​c.*1140A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,198 control chromosomes in the GnomAD database, including 45,605 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 0.76 (45593 hom., cov: 34)
  • Exomes 𝑓: 0.96 (12 hom.)
• Consequence: NOS1AP NM_014697.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

Genes affected

NOS1AP (HGNC:16859): (nitric oxide synthase 1 adaptor protein) This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.*1140A>C		3_prime_UTR_variant	10/10	ENST00000361897.10
NOS1AP	NM_001126060.2	c.*1140A>C		3_prime_UTR_variant	2/2
NOS1AP	NM_001164757.2	c.*1140A>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.*1140A>C		3_prime_UTR_variant	10/10	1	NM_014697.3
NOS1AP	ENST00000493151.1	c.*1140A>C		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115545 AN: 152054 Hom.: 45585 Cov.: 34

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.962 AC: 25 AN: 26 Hom.: 12 Cov.: 0 AF XY: 0.944 AC XY: 17 AN XY: 18

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.760 AC: 115583 AN: 152172 Hom.: 45593 Cov.: 34 AF XY: 0.760 AC XY: 56552 AN XY: 74388

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.794

Alfa AF: 0.804 Hom.: 6336

Bravo AF: 0.745

Asia WGS AF: 0.749 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.80

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: rs164147; hg19: chr1-162338397;