Genetic Variant NOSTRIN:c.-266-57G>T (chr2-168802324-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001171631.2(NOSTRIN):c.-266-57G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 301,072 control chromosomes in the GnomAD database, including 4,716 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 0.18 ( 2936 hom., cov: 32)

Exomes 𝑓: 0.14 ( 1780 hom. )

Consequence

NOSTRIN
NM_001171631.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188

Variant links:

Genes affected

NOSTRIN (HGNC:20203): (nitric oxide synthase trafficking) Nitric oxide (NO) is a potent mediator in biologic processes such as neurotransmission, inflammatory response, and vascular homeostasis. NOSTRIN binds the enzyme responsible for NO production, endothelial NO synthase (ENOS; MIM 163729), and triggers the translocation of ENOS from the plasma membrane to vesicle-like subcellular structures, thereby attenuating ENOS-dependent NO production.[supplied by OMIM, Apr 2004]

NOSTRIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOSTRIN	NM_001171631.2 link	c.-266-57G>T		intron_variant	Intron 4 of 20		NP_001165102.1	Q8IVI9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000444448.6 link	c.-266-57G>T		intron_variant	Intron 2 of 18	5		ENSP00000394051.2		Q8IVI9-4
NOSTRIN	ENST00000458381.6 link	c.-266-57G>T		intron_variant	Intron 4 of 20	2		ENSP00000402140.2		Q8IVI9-4

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27669

AN:

152042

Hom.:

2936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0935

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.138

AC:

20582

AN:

148912

Hom.:

1780

AF XY:

0.134

AC XY:

10443

AN XY:

78200

show subpopulations

Gnomad4 AFR exome

AF:

0.282

Gnomad4 AMR exome

AF:

0.0995

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.00105

Gnomad4 SAS exome

AF:

0.0987

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.182

AC:

27683

AN:

152160

Hom.:

2936

Cov.:

AF XY:

0.177

AC XY:

13170

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0929

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.119

Hom.:

290

Bravo

AF:

0.186

Asia WGS

AF:

0.0800

AC:

278

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

DANN

Benign

0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over