1-162076345-C-G

Variant names:

• chr1-162076345-C-G
• rs1415262
• NM_014697.3:c.105+6063C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.105+6063C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,962 control chromosomes in the GnomAD database, including 21,259 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 0.49 (21259 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 9 publications found

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]

NOS1AP Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.105+6063C>G		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.105+6063C>G		intron_variant	Intron 1 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.105+6063C>G		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.105+6063C>G		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.105+6063C>G		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73970 AN: 151844 Hom.: 21243 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.487 AC: 74008 AN: 151962 Hom.: 21259 Cov.: 31 AF XY: 0.486 AC XY: 36124 AN XY: 74278

African (AFR) AF: 0.185 AC: 7683 AN: 41426

American (AMR) AF: 0.565 AC: 8629 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1549 AN: 5174

South Asian (SAS) AF: 0.345 AC: 1653 AN: 4798

European-Finnish (FIN) AF: 0.636 AC: 6705 AN: 10536

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.648 AC: 44028 AN: 67978

Other (OTH) AF: 0.508 AC: 1069 AN: 2104

Alfa AF: 0.572 Hom.: 3414

Bravo AF: 0.475

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.78
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1415262; hg19: chr1-162046135;