rs3927640

Positions:

• chr1-162186023-G-A

Variant summary

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

The NM_014697.3(NOS1AP):​c.177+31547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,090 control chromosomes in the GnomAD database, including 20,495 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 0.50 (20495 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+31547G>A		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+31547G>A		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+31547G>A		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.177+31547G>A		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.177+31547G>A		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76222 AN: 151972 Hom.: 20477 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.502 AC: 76287 AN: 152090 Hom.: 20495 Cov.: 32 AF XY: 0.503 AC XY: 37377 AN XY: 74324

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.500

Alfa AF: 0.436 Hom.: 1954

Bravo AF: 0.514

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.63

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: rs3927640; hg19: chr1-162155813;