1-162134868-T-C

Variant names:

• chr1-162134868-T-C
• rs1337072
• NM_014697.3:c.106-19537T>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.106-19537T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,102 control chromosomes in the GnomAD database, including 7,847 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 0.24 (7847 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 6 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)

LOC105371475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-19537T>C		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-19537T>C		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.487-1742A>G		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.487-20966A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-19537T>C		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-19537T>C		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-19537T>C		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35720 AN: 151984 Hom.: 7827 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.235 AC: 35784 AN: 152102 Hom.: 7847 Cov.: 32 AF XY: 0.229 AC XY: 17011 AN XY: 74374

African (AFR) AF: 0.586 AC: 24290 AN: 41426

American (AMR) AF: 0.121 AC: 1852 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.177 AC: 916 AN: 5180

South Asian (SAS) AF: 0.0830 AC: 400 AN: 4820

European-Finnish (FIN) AF: 0.0797 AC: 844 AN: 10588

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6626 AN: 68004

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.120 Hom.: 2618

Bravo AF: 0.253

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.15
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: rs1337072; hg19: chr1-162104658; COSMIC: COSV107450619;