ENST00000493151:c.-1040T>C

Variant names:

• chr1-162364310-T-C
• rs905720
• ENST00000493151:c.-1040T>C

Variant summary

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

The ENST00000493151(NOS1AP):​c.-1040T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 985,162 control chromosomes in the GnomAD database, including 249,549 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 0.65 (33046 hom., cov: 32)
  • Exomes 𝑓: 0.72 (216503 hom.)
• Consequence: NOS1AP ENST00000493151 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.940-1094T>C		intron_variant	Intron 8 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001126060.2	c.-1040T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NP_001119532.2
NOS1AP	NM_001126060.2	c.-1040T>C		5_prime_UTR_variant	Exon 1 of 2		NP_001119532.2
NOS1AP	NM_001164757.2	c.925-1094T>C		intron_variant	Intron 8 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.940-1094T>C		intron_variant	Intron 8 of 9	1	NM_014697.3	ENSP00000355133.5

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98301 AN: 151938 Hom.: 33041 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.719 AC: 599306 AN: 833106 Hom.: 216503 Cov.: 40 AF XY: 0.719 AC XY: 276559 AN XY: 384716

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.772

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.647 AC: 98327 AN: 152056 Hom.: 33046 Cov.: 32 AF XY: 0.646 AC XY: 48045 AN XY: 74342

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.697

Alfa AF: 0.708 Hom.: 38277

Bravo AF: 0.639

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.84

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: rs905720; hg19: chr1-162334100;