chr1-162368587-C-G

Variant names:

• chr1-162368587-C-G
• rs164146
• NM_014697.3:c.*1120C>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.*1120C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,276 control chromosomes in the GnomAD database, including 45,621 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 (45607 hom., cov: 35)
  • Exomes 𝑓: 0.85 (14 hom.)
• Consequence: NOS1AP NM_014697.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.*1120C>G		3_prime_UTR	Exon 10 of 10	NP_055512.1
	NOS1AP	NM_001164757.2		c.*1120C>G		3_prime_UTR	Exon 10 of 10	NP_001158229.1
	NOS1AP	NM_001126060.2		c.*1120C>G		3_prime_UTR	Exon 2 of 2	NP_001119532.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.*1120C>G		3_prime_UTR	Exon 10 of 10	ENSP00000355133.5
	NOS1AP	ENST00000493151.1	TSL:1	c.*1120C>G		3_prime_UTR	Exon 2 of 2	ENSP00000434988.1
	ENSG00000254706	ENST00000420220.1	TSL:5	c.-12+1383C>G		intron	N/A	ENSP00000398035.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115580 AN: 152118 Hom.: 45599 Cov.: 35

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.850 AC: 34 AN: 40 Hom.: 14 Cov.: 0 AF XY: 0.853 AC XY: 29 AN XY: 34

African (AFR) AF: 0.500 AC: 1 AN: 2

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: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.867 AC: 26 AN: 30

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.759 AC: 115618 AN: 152236 Hom.: 45607 Cov.: 35 AF XY: 0.760 AC XY: 56575 AN XY: 74428

African (AFR) AF: 0.531 AC: 22038 AN: 41512

American (AMR) AF: 0.816 AC: 12492 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3470

East Asian (EAS) AF: 0.850 AC: 4401 AN: 5180

South Asian (SAS) AF: 0.724 AC: 3496 AN: 4826

European-Finnish (FIN) AF: 0.881 AC: 9351 AN: 10610

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

European-Non Finnish (NFE) AF: 0.855 AC: 58174 AN: 68014

Other (OTH) AF: 0.794 AC: 1679 AN: 2114

Alfa AF: 0.803 Hom.: 6228

Bravo AF: 0.745

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.93
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: rs164146; hg19: chr1-162338377;