NM_001171631.2:c.-266-57G>T

Variant names:

• chr2-168802324-G-T
• rs829957
• NM_001171631.2:c.-266-57G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171631.2(NOSTRIN):​c.-266-57G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 301,072 control chromosomes in the GnomAD database, including 4,716 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 0.18 (2936 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1780 hom.)
• Consequence: NOSTRIN NM_001171631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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.-266-57G>T		intron	N/A	NP_001165102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOSTRIN	ENST00000444448.6	TSL:5	c.-266-57G>T		intron	N/A	ENSP00000394051.2
	NOSTRIN	ENST00000458381.6	TSL:2	c.-266-57G>T		intron	N/A	ENSP00000402140.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27669 AN: 152042 Hom.: 2936 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.138 AC: 20582 AN: 148912 Hom.: 1780 AF XY: 0.134 AC XY: 10443 AN XY: 78200

African (AFR) AF: 0.282 AC: 1479 AN: 5248

American (AMR) AF: 0.0995 AC: 790 AN: 7938

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 692 AN: 4188

East Asian (EAS) AF: 0.00105 AC: 10 AN: 9534

South Asian (SAS) AF: 0.0987 AC: 1857 AN: 18812

European-Finnish (FIN) AF: 0.132 AC: 890 AN: 6764

Middle Eastern (MID) AF: 0.145 AC: 91 AN: 628

European-Non Finnish (NFE) AF: 0.155 AC: 13540 AN: 87188

Other (OTH) AF: 0.143 AC: 1233 AN: 8612

GnomAD4 genome AF: 0.182 AC: 27683 AN: 152160 Hom.: 2936 Cov.: 32 AF XY: 0.177 AC XY: 13170 AN XY: 74394

African (AFR) AF: 0.288 AC: 11933 AN: 41492

American (AMR) AF: 0.123 AC: 1878 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5182

South Asian (SAS) AF: 0.0929 AC: 448 AN: 4820

European-Finnish (FIN) AF: 0.126 AC: 1340 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10938 AN: 67986

Other (OTH) AF: 0.186 AC: 394 AN: 2116

Alfa AF: 0.124 Hom.: 319

Bravo AF: 0.186

Asia WGS AF: 0.0800 AC: 278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.19
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs829957; hg19: chr2-169658834;