chr1-162154155-G-C

Position:

• chr1-162154155-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014697.3(NOS1AP):​c.106-250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,938 control chromosomes in the GnomAD database, including 5,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5741 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-162154155-G-C is Benign according to our data. Variant chr1-162154155-G-C is described in ClinVar as [Benign]. Clinvar id is 1222171.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.106-250G>C		intron_variant		ENST00000361897.10
LOC105371475	XR_007066699.1	n.486+14127C>G		intron_variant, non_coding_transcript_variant
NOS1AP	NM_001164757.2	c.106-250G>C		intron_variant
LOC105371475	XR_007066697.1	n.486+14127C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-250G>C		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.106-250G>C		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.106-250G>C		intron_variant, NMD_transcript_variant		1
	ENST00000648032.1	n.439-6437C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39614 AN: 151820 Hom.: 5736 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39627 AN: 151938 Hom.: 5741 Cov.: 31 AF XY: 0.269 AC XY: 19987 AN XY: 74242

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.248

Alfa AF: 0.102 Hom.: 143

Bravo AF: 0.254

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.73

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: rs10918776; hg19: chr1-162123945;