2-168802434-A-C

Variant names:

• chr2-168802434-A-C
• rs6433093
• NM_001171631.2:c.-213A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171631.2. 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_001171631.2		c.-213A>C		5_prime_UTR	Exon 5 of 21	NP_001165102.1
	NOSTRIN	NM_001039724.4	MANE Select	c.-213A>C		upstream_gene	N/A	NP_001034813.2
	NOSTRIN	NM_001171632.2		c.-213A>C		upstream_gene	N/A	NP_001165103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000444448.6	TSL:5	c.-213A>C		5_prime_UTR	Exon 3 of 19	ENSP00000394051.2
	NOSTRIN	ENST00000458381.6	TSL:2	c.-213A>C		5_prime_UTR	Exon 5 of 21	ENSP00000402140.2
	NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.-213A>C		upstream_gene	N/A	ENSP00000318921.7

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.050
DANN	Benign	0.46
PhyloP100		-1.7
PromoterAI		0.0099	Neutral
Mutation Taster		=300/0	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: rs6433093; hg19: chr2-169658944;