NM_001039724.4:c.113+4717C>T

Variant names:

• chr2-168816369-C-T
• rs7583629
• NM_001039724.4:c.113+4717C>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.113+4717C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,028 control chromosomes in the GnomAD database, including 3,537 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 0.20 (3537 hom., cov: 32)
• Consequence: NOSTRIN NM_001039724.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 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.113+4717C>T		intron	N/A	NP_001034813.2
	NOSTRIN	NM_001171631.2		c.113+4717C>T		intron	N/A	NP_001165102.1
	NOSTRIN	NM_001171632.2		c.113+4717C>T		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.113+4717C>T		intron	N/A	ENSP00000318921.7
	NOSTRIN	ENST00000397209.6	TSL:1	c.113+4717C>T		intron	N/A	ENSP00000380392.2
	NOSTRIN	ENST00000397206.6	TSL:1	c.-121-8265C>T		intron	N/A	ENSP00000380390.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30930 AN: 151910 Hom.: 3527 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.204 AC: 30977 AN: 152028 Hom.: 3537 Cov.: 32 AF XY: 0.201 AC XY: 14957 AN XY: 74322

African (AFR) AF: 0.261 AC: 10815 AN: 41448

American (AMR) AF: 0.283 AC: 4321 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5180

South Asian (SAS) AF: 0.0921 AC: 443 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1509 AN: 10570

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12392 AN: 67968

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.193 Hom.: 2455

Bravo AF: 0.218

Asia WGS AF: 0.0930 AC: 323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.68
DANN	Benign	0.84
PhyloP100		-0.57
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: rs7583629; hg19: chr2-169672879;