rs3918227

Variant names:

• chr7-151003858-C-A
• rs3918227
• ENST00000484524.5:c.*570C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151003858-C-A
• chr7-151003858-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001160111.1(NOS3):​c.*570C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 396,480 control chromosomes in the GnomAD database, including 1,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (491 hom., cov: 32)
  • Exomes 𝑓: 0.083 (946 hom.)
• Consequence: NOS3 NM_001160111.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.968
• Publications: 47 publications found

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-151003858-C-A is Benign according to our data. Variant chr7-151003858-C-A is described in ClinVar as Benign. ClinVar VariationId is 1227867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160111.1. 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
	NOS3	NM_000603.5	MANE Select	c.1752+1554C>A		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.*570C>A		3_prime_UTR	Exon 14 of 14	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.*455C>A		3_prime_UTR	Exon 14 of 14	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000484524.5	TSL:1	c.*570C>A		3_prime_UTR	Exon 14 of 14	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.*455C>A		3_prime_UTR	Exon 14 of 14	ENSP00000420551.1	P29474-3
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+1554C>A		intron	N/A	ENSP00000297494.3	P29474-1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10400 AN: 151996 Hom.: 492 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0825 AC: 20166 AN: 244366 Hom.: 946 Cov.: 0 AF XY: 0.0821 AC XY: 11088 AN XY: 135092

African (AFR) AF: 0.0167 AC: 120 AN: 7192

American (AMR) AF: 0.0492 AC: 1051 AN: 21382

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 100 AN: 7048

East Asian (EAS) AF: 0.0717 AC: 611 AN: 8516

South Asian (SAS) AF: 0.0750 AC: 3658 AN: 48782

European-Finnish (FIN) AF: 0.132 AC: 1724 AN: 13084

Middle Eastern (MID) AF: 0.0648 AC: 80 AN: 1234

European-Non Finnish (NFE) AF: 0.0953 AC: 11965 AN: 125546

Other (OTH) AF: 0.0740 AC: 857 AN: 11582

GnomAD4 genome AF: 0.0683 AC: 10393 AN: 152114 Hom.: 491 Cov.: 32 AF XY: 0.0703 AC XY: 5227 AN XY: 74362

African (AFR) AF: 0.0174 AC: 722 AN: 41490

American (AMR) AF: 0.0510 AC: 780 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.0717 AC: 372 AN: 5188

South Asian (SAS) AF: 0.0623 AC: 300 AN: 4814

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10560

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6489 AN: 67992

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0800 Hom.: 1207

Bravo AF: 0.0583

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.72
PhyloP100		0.97
Mutation Taster		=100/0	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: rs3918227; hg19: chr7-150700946;