rs1337072

Positions:

• chr1-162134868-T-C

Variant summary

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

The ENST00000361897.10(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 ENST00000361897.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.93).
• 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/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-19537T>C		intron_variant		ENST00000361897.10	NP_055512.1
LOC105371475	XR_007066699.1	n.487-20966A>G		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-19537T>C		intron_variant			NP_001158229.1
LOC105371475	XR_007066697.1	n.487-1742A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-19537T>C		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.106-19537T>C		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.106-19537T>C		intron_variant, NMD_transcript_variant		1		ENSP00000396713

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

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0830

Gnomad4 FIN AF: 0.0797

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.191

Alfa AF: 0.112 Hom.: 1857

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

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: rs1337072; hg19: chr1-162104658;