rs12993143

Variant names:

• chr2-168862990-T-G
• rs12993143
• NM_001039724.4:c.1384+941T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039724.4(NOSTRIN):​c.1384+941T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 149,478 control chromosomes in the GnomAD database, including 11,283 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 0.38 (11283 hom., cov: 32)
• Consequence: NOSTRIN NM_001039724.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 1 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]

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 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.1384+941T>G		intron	N/A	NP_001034813.2	Q8IVI9-1
	NOSTRIN	NM_001171631.2		c.1555+941T>G		intron	N/A	NP_001165102.1	Q8IVI9-4
	NOSTRIN	NM_001171632.2		c.1300+941T>G		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.1384+941T>G		intron	N/A	ENSP00000318921.7	Q8IVI9-1
	NOSTRIN	ENST00000397209.6	TSL:1	c.1300+941T>G		intron	N/A	ENSP00000380392.2	Q8IVI9-2
	NOSTRIN	ENST00000397206.6	TSL:1	c.1150+941T>G		intron	N/A	ENSP00000380390.2	Q8IVI9-3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 56773 AN: 149360 Hom.: 11273 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.380 AC: 56800 AN: 149478 Hom.: 11283 Cov.: 32 AF XY: 0.378 AC XY: 27548 AN XY: 72948

African (AFR) AF: 0.280 AC: 11094 AN: 39692

American (AMR) AF: 0.319 AC: 4778 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1298 AN: 3462

East Asian (EAS) AF: 0.270 AC: 1374 AN: 5084

South Asian (SAS) AF: 0.292 AC: 1366 AN: 4684

European-Finnish (FIN) AF: 0.469 AC: 4901 AN: 10456

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30520 AN: 67826

Other (OTH) AF: 0.394 AC: 822 AN: 2086

Alfa AF: 0.384 Hom.: 2027

Bravo AF: 0.359

Asia WGS AF: 0.297 AC: 1031 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12993143; hg19: chr2-169719500;