1-162138329-A-G

Position:

• chr1-162138329-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000361897.10(NOS1AP):​c.106-16076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,960 control chromosomes in the GnomAD database, including 37,076 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 0.69 (37076 hom., cov: 31)
• Consequence: NOS1AP ENST00000361897.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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]

LOC105371475 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-16076A>G		intron_variant		ENST00000361897.10	NP_055512.1
LOC105371475	XR_007066699.1	n.487-24427T>C		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-16076A>G		intron_variant			NP_001158229.1
LOC105371475	XR_007066697.1	n.487-5203T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-16076A>G		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.106-16076A>G		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.106-16076A>G		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105420 AN: 151842 Hom.: 37027 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.694 AC: 105522 AN: 151960 Hom.: 37076 Cov.: 31 AF XY: 0.688 AC XY: 51075 AN XY: 74276

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.680

Alfa AF: 0.710 Hom.: 77833

Bravo AF: 0.700

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.74

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: rs4657154; hg19: chr1-162108119;