rs7540690

Variant names:

• chr1-162144427-G-A
• rs7540690
• NM_014697.3:c.106-9978G>A

Variant summary

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

The NM_014697.3(NOS1AP):​c.106-9978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,180 control chromosomes in the GnomAD database, including 4,491 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 (4491 hom., cov: 34)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-9978G>A		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-9978G>A		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.487-11301C>T		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+23855C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-9978G>A		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-9978G>A		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-9978G>A		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32765 AN: 152066 Hom.: 4489 Cov.: 34

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.215 AC: 32759 AN: 152180 Hom.: 4491 Cov.: 34 AF XY: 0.225 AC XY: 16719 AN XY: 74404

African (AFR) AF: 0.0926 AC: 3849 AN: 41546

American (AMR) AF: 0.264 AC: 4043 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2673 AN: 5170

South Asian (SAS) AF: 0.549 AC: 2642 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2725 AN: 10584

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 14992 AN: 67988

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.226 Hom.: 2697

Bravo AF: 0.202

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		0.82
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: rs7540690; hg19: chr1-162114217;