2-168802434-A-C

Position:

• chr2-168802434-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOSTRIN	NM_001171631.2	c.-213A>C		5_prime_UTR_variant	5/21		NP_001165102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000444448.6	c.-213A>C		5_prime_UTR_variant	3/19	5		ENSP00000394051
NOSTRIN	ENST00000458381.6	c.-213A>C		5_prime_UTR_variant	5/21	2		ENSP00000402140

Frequencies

GnomAD3 genomes AF: 0.699 AC: 105987 AN: 151734 Hom.: 37596 Cov.: 30

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.: 0 AF XY: 0.752 AC XY: 148915 AN XY: 197914

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.972

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.778

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome AF: 0.699 AC: 106076 AN: 151852 Hom.: 37629 Cov.: 30 AF XY: 0.708 AC XY: 52526 AN XY: 74236

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.682

Alfa AF: 0.701 Hom.: 6728

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
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs6433093; hg19: chr2-169658944;