rs7540690

Positions:

• chr1-162144427-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.106-9978G>A		intron_variant		ENST00000361897.10
LOC105371475	XR_007066699.1	n.486+23855C>T		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-9978G>A		intron_variant
LOC105371475	XR_007066697.1	n.487-11301C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-9978G>A		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.106-9978G>A		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.106-9978G>A		intron_variant, NMD_transcript_variant		1

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

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.232

Alfa AF: 0.222 Hom.: 1170

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

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: rs7540690; hg19: chr1-162114217;