chr1-162365634-T-C

Position:

• chr1-162365634-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014697.3(NOS1AP):​c.1105+65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,591,912 control chromosomes in the GnomAD database, including 584,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (47140 hom., cov: 33)
  • Exomes 𝑓: 0.86 (537781 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38

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]

ENSG00000254706 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-162365634-T-C is Benign according to our data. Variant chr1-162365634-T-C is described in ClinVar as [Benign]. Clinvar id is 1251683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.1105+65T>C		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.1090+65T>C		intron_variant			NP_001158229.1
NOS1AP	NM_001126060.2	c.220+65T>C		intron_variant			NP_001119532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.1105+65T>C		intron_variant		1	NM_014697.3	ENSP00000355133.5

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117132 AN: 152020 Hom.: 47137 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.803

GnomAD4 exome AF: 0.861 AC: 1239575 AN: 1439772 Hom.: 537781 AF XY: 0.857 AC XY: 613868 AN XY: 716360

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.706

Gnomad4 FIN exome AF: 0.894

Gnomad4 NFE exome AF: 0.886

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.770 AC: 117159 AN: 152140 Hom.: 47140 Cov.: 33 AF XY: 0.768 AC XY: 57157 AN XY: 74394

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.797

Alfa AF: 0.840 Hom.: 26631

Bravo AF: 0.755

Asia WGS AF: 0.731 AC: 2542 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.69

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: rs1964052; hg19: chr1-162335424;