rs76662883

Positions:

• chr1-162119528-G-A
• chr1-162119528-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014697.3(NOS1AP):​c.106-34877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 152,278 control chromosomes in the GnomAD database, including 12 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 0.0087 (12 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-34877G>A		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-34877G>A		intron_variant			NP_001158229.1
LOC105371475	XR_007066699.1	n.487-5626C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-34877G>A		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-34877G>A		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-34877G>A		intron_variant		1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1324 AN: 152160 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.00860

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

GnomAD4 genome AF: 0.00869 AC: 1324 AN: 152278 Hom.: 12 Cov.: 32 AF XY: 0.00810 AC XY: 603 AN XY: 74450

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00660 Hom.: 0

Bravo AF: 0.00814

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.82

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: rs76662883; hg19: chr1-162089318;