Genetic Variant NOSTRIN:c.-213A>T (chr2-168802434-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001171631.2(NOSTRIN):c.-213A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000802 in 374,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)

Exomes 𝑓: 0.0000080 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000802

AC:

AN:

374070

Hom.:

Cov.:

AF XY:

0.00000504

AC XY:

AN XY:

198348

show subpopulations

African (AFR)

AF:

0.0000952

AC:

AN:

10506

American (AMR)

AF:

0.00

AC:

AN:

17814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10958

East Asian (EAS)

AF:

0.00

AC:

AN:

23534

South Asian (SAS)

AF:

0.00

AC:

AN:

43624

European-Finnish (FIN)

AF:

0.0000320

AC:

AN:

31278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1534

European-Non Finnish (NFE)

AF:

0.00000467

AC:

AN:

214280

Other (OTH)

AF:

0.00

AC:

AN:

20542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.047

(source)

DANN

Benign

0.30

PhyloP100

-1.7

PromoterAI

0.055

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over