rs76204833

Positions:

• chr1-162128539-A-C
• chr1-162128539-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.106-25866A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 152,230 control chromosomes in the GnomAD database, including 283 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 0.057 (283 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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 -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 = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-25866A>C		intron_variant		ENST00000361897.10	NP_055512.1
LOC105371475	XR_007066699.1	n.487-14637T>G		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-25866A>C		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-25866A>C		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.106-25866A>C		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.106-25866A>C		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8598 AN: 152112 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0565 AC: 8602 AN: 152230 Hom.: 283 Cov.: 32 AF XY: 0.0554 AC XY: 4128 AN XY: 74458

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0612 Hom.: 94

Bravo AF: 0.0539

Asia WGS AF: 0.0230 AC: 78 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.83

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: rs76204833; hg19: chr1-162098329;