NM_001039724.4:c.114-5099G>A

Variant names:

• chr2-168819535-G-A
• rs482435
• NM_001039724.4:c.114-5099G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	NM_001039724.4	MANE Select	c.114-5099G>A		intron	N/A	NP_001034813.2
	NOSTRIN	NM_001171631.2		c.114-5099G>A		intron	N/A	NP_001165102.1
	NOSTRIN	NM_001171632.2		c.113+7883G>A		intron	N/A	NP_001165103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.114-5099G>A		intron	N/A	ENSP00000318921.7
	NOSTRIN	ENST00000397209.6	TSL:1	c.113+7883G>A		intron	N/A	ENSP00000380392.2
	NOSTRIN	ENST00000397206.6	TSL:1	c.-121-5099G>A		intron	N/A	ENSP00000380390.2

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

African (AFR) AF: 0.603 AC: 24980 AN: 41444

American (AMR) AF: 0.730 AC: 11164 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2398 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4541 AN: 5168

South Asian (SAS) AF: 0.831 AC: 4009 AN: 4824

European-Finnish (FIN) AF: 0.771 AC: 8159 AN: 10580

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.682 AC: 46392 AN: 67976

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.681 Hom.: 46551

Bravo AF: 0.673

Asia WGS AF: 0.828 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.77
PhyloP100		-0.72
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: rs482435; hg19: chr2-169676045;