rs549582

chr2-168833579-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039724.4(NOSTRIN):c.406-648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,252 control chromosomes in the GnomAD database, including 59,872 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 0.89 (59872 hom., cov: 32)
• Consequence: NOSTRIN NM_001039724.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOSTRIN	NM_001039724.4	c.406-648C>T		intron_variant		ENST00000317647.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOSTRIN	ENST00000317647.12	c.406-648C>T		intron_variant		1	NM_001039724.4	P1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134663 AN: 152134 Hom.: 59812 Cov.: 32

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.885 AC: 134784 AN: 152252 Hom.: 59872 Cov.: 32 AF XY: 0.890 AC XY: 66247 AN XY: 74450

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.867

Alfa AF: 0.844 Hom.: 40752

Bravo AF: 0.884

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.61
Dann	Benign	0.24

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: rs549582; hg19: chr2-169690089;