1-162148256-T-C

Variant names:

• chr1-162148256-T-C
• rs1932933
• NM_014697.3:c.106-6149T>C

Variant summary

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

The NM_014697.3(NOS1AP):​c.106-6149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,098 control chromosomes in the GnomAD database, including 21,098 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 (21098 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 16 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)

ENSG00000285636 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-6149T>C		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-6149T>C		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.487-15130A>G		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+20026A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-6149T>C		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-6149T>C		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-6149T>C		intron_variant	Intron 1 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.439-538A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75514 AN: 151980 Hom.: 21085 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.497 AC: 75542 AN: 152098 Hom.: 21098 Cov.: 32 AF XY: 0.495 AC XY: 36792 AN XY: 74362

African (AFR) AF: 0.254 AC: 10537 AN: 41482

American (AMR) AF: 0.589 AC: 9014 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1256 AN: 5160

South Asian (SAS) AF: 0.337 AC: 1628 AN: 4826

European-Finnish (FIN) AF: 0.606 AC: 6428 AN: 10612

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43059 AN: 67944

Other (OTH) AF: 0.540 AC: 1138 AN: 2108

Alfa AF: 0.557 Hom.: 23980

Bravo AF: 0.491

Asia WGS AF: 0.315 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.82
PhyloP100		0.19
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: rs1932933; hg19: chr1-162118046;