rs164147

Variant names:

• chr1-162368607-A-C
• rs164147
• NM_014697.3:c.*1140A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-162368607-A-C
• chr1-162368607-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.*1140A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,198 control chromosomes in the GnomAD database, including 45,605 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 0.76 (45593 hom., cov: 34)
  • Exomes 𝑓: 0.96 (12 hom.)
• Consequence: NOS1AP NM_014697.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.*1140A>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.*1140A>C		3_prime_UTR_variant	Exon 10 of 10		NP_001158229.1
NOS1AP	NM_001126060.2	c.*1140A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001119532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.*1140A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_014697.3	ENSP00000355133.5
ENSG00000254706	ENST00000420220.1	c.-12+1403A>C		intron_variant	Intron 2 of 3	5		ENSP00000398035.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115545 AN: 152054 Hom.: 45585 Cov.: 34

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.962 AC: 25 AN: 26 Hom.: 12 Cov.: 0 AF XY: 0.944 AC XY: 17 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 18 AN: 18

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.760 AC: 115583 AN: 152172 Hom.: 45593 Cov.: 34 AF XY: 0.760 AC XY: 56552 AN XY: 74388

African (AFR) AF: 0.531 AC: 22019 AN: 41480

American (AMR) AF: 0.816 AC: 12489 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2922 AN: 3466

East Asian (EAS) AF: 0.850 AC: 4398 AN: 5172

South Asian (SAS) AF: 0.725 AC: 3497 AN: 4826

European-Finnish (FIN) AF: 0.882 AC: 9350 AN: 10602

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58169 AN: 68008

Other (OTH) AF: 0.794 AC: 1678 AN: 2114

Alfa AF: 0.813 Hom.: 13517

Bravo AF: 0.745

Asia WGS AF: 0.749 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		0.42
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: rs164147; hg19: chr1-162338397;