1-162365634-T-C

Variant names:

• chr1-162365634-T-C
• rs1964052
• NM_014697.3:c.1105+65T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

NOS1AP Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000254706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.1105+65T>C		intron_variant	Intron 9 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.1090+65T>C		intron_variant	Intron 9 of 9		NP_001158229.1
NOS1AP	NM_001126060.2	c.220+65T>C		intron_variant	Intron 1 of 1		NP_001119532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.1105+65T>C		intron_variant	Intron 9 of 9	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

African (AFR) AF: 0.504 AC: 16748 AN: 33262

American (AMR) AF: 0.794 AC: 34930 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 22039 AN: 25972

East Asian (EAS) AF: 0.868 AC: 34343 AN: 39556

South Asian (SAS) AF: 0.706 AC: 60005 AN: 84950

European-Finnish (FIN) AF: 0.894 AC: 35368 AN: 39566

Middle Eastern (MID) AF: 0.808 AC: 3461 AN: 4282

European-Non Finnish (NFE) AF: 0.886 AC: 982308 AN: 1108198

Other (OTH) AF: 0.840 AC: 50373 AN: 59988

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

African (AFR) AF: 0.516 AC: 21373 AN: 41428

American (AMR) AF: 0.823 AC: 12597 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4426 AN: 5170

South Asian (SAS) AF: 0.698 AC: 3368 AN: 4824

European-Finnish (FIN) AF: 0.885 AC: 9385 AN: 10606

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60344 AN: 68028

Other (OTH) AF: 0.797 AC: 1681 AN: 2108

Alfa AF: 0.839 Hom.: 29627

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

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.69
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1964052; hg19: chr1-162335424;