rs482435

Positions:

• chr2-168819535-G-A
• chr2-168819535-G-T

Variant summary

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

The NM_001039724.4(NOSTRIN):​c.114-5099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,068 control chromosomes in the GnomAD database, including 35,890 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 0.68 (35890 hom., cov: 32)
• Consequence: NOSTRIN NM_001039724.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOSTRIN	NM_001039724.4	c.114-5099G>A		intron_variant		ENST00000317647.12	NP_001034813.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000317647.12	c.114-5099G>A		intron_variant		1	NM_001039724.4	ENSP00000318921.7

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103881 AN: 151950 Hom.: 35862 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.684 AC: 103962 AN: 152068 Hom.: 35890 Cov.: 32 AF XY: 0.693 AC XY: 51542 AN XY: 74336

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.675

Alfa AF: 0.683 Hom.: 35787

Bravo AF: 0.673

Asia WGS AF: 0.828 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.77

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: rs482435; hg19: chr2-169676045;