2-168833579-C-T

Variant names:

• chr2-168833579-C-T
• rs549582
• NM_001039724.4:c.406-648C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	NM_001039724.4	MANE Select	c.406-648C>T		intron	N/A	NP_001034813.2	Q8IVI9-1
	NOSTRIN	NM_001171631.2		c.406-648C>T		intron	N/A	NP_001165102.1	Q8IVI9-4
	NOSTRIN	NM_001171632.2		c.322-648C>T		intron	N/A	NP_001165103.1	Q8IVI9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.406-648C>T		intron	N/A	ENSP00000318921.7	Q8IVI9-1
	NOSTRIN	ENST00000397209.6	TSL:1	c.322-648C>T		intron	N/A	ENSP00000380392.2	Q8IVI9-2
	NOSTRIN	ENST00000397206.6	TSL:1	c.172-648C>T		intron	N/A	ENSP00000380390.2	Q8IVI9-3

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

African (AFR) AF: 0.965 AC: 40081 AN: 41534

American (AMR) AF: 0.854 AC: 13069 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2867 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4966 AN: 5182

South Asian (SAS) AF: 0.953 AC: 4603 AN: 4830

European-Finnish (FIN) AF: 0.890 AC: 9449 AN: 10614

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56802 AN: 68000

Other (OTH) AF: 0.867 AC: 1832 AN: 2114

Alfa AF: 0.853 Hom.: 67475

Bravo AF: 0.884

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.24
PhyloP100		-0.12
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: rs549582; hg19: chr2-169690089;