rs10918762

Positions:

• chr1-162149194-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.106-5211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,148 control chromosomes in the GnomAD database, including 5,715 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 0.26 (5715 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.106-5211A>G		intron_variant		ENST00000361897.10
LOC105371475	XR_007066699.1	n.486+19088T>C		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-5211A>G		intron_variant
LOC105371475	XR_007066697.1	n.487-16068T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-5211A>G		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.106-5211A>G		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.106-5211A>G		intron_variant, NMD_transcript_variant		1
	ENST00000648032.1	n.439-1476T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39340 AN: 152030 Hom.: 5712 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.259 AC: 39336 AN: 152148 Hom.: 5715 Cov.: 33 AF XY: 0.267 AC XY: 19862 AN XY: 74360

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.244

Alfa AF: 0.223 Hom.: 6803

Bravo AF: 0.251

Asia WGS AF: 0.509 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.45

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: rs10918762; hg19: chr1-162118984;