dbSNP rs6433093: NOSTRIN:c.-213A>C (chr2-168802434-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001171631.2(NOSTRIN):c.-213A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 525,050 control chromosomes in the GnomAD database, including 142,855 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 0.70 ( 37629 hom., cov: 30)

Exomes 𝑓: 0.75 ( 105226 hom. )

Consequence

NOSTRIN
NM_001171631.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

6 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOSTRIN	NM_001039724.4 link	c.-213A>C		upstream_gene_variant		ENST00000317647.12	NP_001034813.2	Q8IVI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000317647.12 link	c.-213A>C		upstream_gene_variant		1	NM_001039724.4	ENSP00000318921.7		Q8IVI9-1

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

105987

AN:

151734

Hom.:

37596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.975

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.789

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.681

GnomAD4 exome

AF:

0.746

AC:

278346

AN:

373198

Hom.:

105226

Cov.:

AF XY:

0.752

AC XY:

148915

AN XY:

197914

show subpopulations

African (AFR)

AF:

0.596

AC:

6226

AN:

10454

American (AMR)

AF:

0.766

AC:

13615

AN:

17782

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

7663

AN:

10938

East Asian (EAS)

AF:

0.972

AC:

22866

AN:

23524

South Asian (SAS)

AF:

0.835

AC:

36391

AN:

43582

European-Finnish (FIN)

AF:

0.778

AC:

24260

AN:

31186

Middle Eastern (MID)

AF:

0.702

AC:

1072

AN:

1526

European-Non Finnish (NFE)

AF:

0.708

AC:

151306

AN:

213716

Other (OTH)

AF:

0.729

AC:

14947

AN:

20490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3210

6419

9629

12838

16048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.699

AC:

106076

AN:

151852

Hom.:

37629

Cov.:

AF XY:

0.708

AC XY:

52526

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.590

AC:

24367

AN:

41320

American (AMR)

AF:

0.743

AC:

11343

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

2456

AN:

3460

East Asian (EAS)

AF:

0.974

AC:

5040

AN:

5172

South Asian (SAS)

AF:

0.840

AC:

4030

AN:

4796

European-Finnish (FIN)

AF:

0.789

AC:

8339

AN:

10574

Middle Eastern (MID)

AF:

0.693

AC:

201

AN:

290

European-Non Finnish (NFE)

AF:

0.708

AC:

48099

AN:

67954

Other (OTH)

AF:

0.682

AC:

1439

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1584

3167

4751

6334

7918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.698

Hom.:

6872

Bravo

AF:

0.688

Asia WGS

AF:

0.871

AC:

3026

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.050

(source)

DANN

Benign

0.46

PhyloP100

-1.7

PromoterAI

0.0099

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over