2-168802434-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• 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: 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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	NM_001171631.2		c.-213A>T		5_prime_UTR	Exon 5 of 21	NP_001165102.1	Q8IVI9-4
	NOSTRIN	NM_001039724.4	MANE Select	c.-213A>T		upstream_gene	N/A	NP_001034813.2	Q8IVI9-1
	NOSTRIN	NM_001171632.2		c.-213A>T		upstream_gene	N/A	NP_001165103.1	Q8IVI9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000444448.6	TSL:5	c.-213A>T		5_prime_UTR	Exon 3 of 19	ENSP00000394051.2	Q8IVI9-4
	NOSTRIN	ENST00000458381.6	TSL:2	c.-213A>T		5_prime_UTR	Exon 5 of 21	ENSP00000402140.2	Q8IVI9-4
	NOSTRIN	ENST00000317647.12	TSL:1 MANE Select	c.-213A>T		upstream_gene	N/A	ENSP00000318921.7	Q8IVI9-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000802 AC: 3 AN: 374070 Hom.: 0 Cov.: 0 AF XY: 0.00000504 AC XY: 1 AN XY: 198348

African (AFR) AF: 0.0000952 AC: 1 AN: 10506

American (AMR) AF: 0.00 AC: 0 AN: 17814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10958

East Asian (EAS) AF: 0.00 AC: 0 AN: 23534

South Asian (SAS) AF: 0.00 AC: 0 AN: 43624

European-Finnish (FIN) AF: 0.0000320 AC: 1 AN: 31278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1534

European-Non Finnish (NFE) AF: 0.00000467 AC: 1 AN: 214280

Other (OTH) AF: 0.00 AC: 0 AN: 20542

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.047
DANN	Benign	0.30
PhyloP100		-1.7
PromoterAI		0.055	Neutral

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;