1-162160691-G-C

Position:

• chr1-162160691-G-C

Variant summary

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

The NM_014697.3(NOS1AP):​c.177+6215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,052 control chromosomes in the GnomAD database, including 3,934 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 0.22 (3934 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.177+6215G>C		intron_variant		ENST00000361897.10
LOC105371475	XR_007066699.1	n.486+7591C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+6215G>C		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.177+6215G>C		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.177+6215G>C		intron_variant, NMD_transcript_variant		1
	ENST00000648032.1	n.438+7591C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34089 AN: 151934 Hom.: 3935 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.224 AC: 34105 AN: 152052 Hom.: 3934 Cov.: 32 AF XY: 0.220 AC XY: 16355 AN XY: 74294

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.221

Alfa AF: 0.234 Hom.: 577

Bravo AF: 0.227

Asia WGS AF: 0.163 AC: 572 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	1.0
DANN	Benign	0.48

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: rs1538018; hg19: chr1-162130481;