7-151002162-G-T

Variant names:

• chr7-151002162-G-T
• rs1800782
• NM_000603.5:c.1648-38G>T

Variant summary

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

The NM_000603.5(NOS3):​c.1648-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,468,152 control chromosomes in the GnomAD database, including 5,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (977 hom., cov: 31)
  • Exomes 𝑓: 0.080 (4804 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24
• Publications: 8 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=-0.92).
• BP6: Variant 7-151002162-G-T is Benign according to our data. Variant chr7-151002162-G-T is described in ClinVar as Benign. ClinVar VariationId is 1227505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. 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
	NOS3	NM_000603.5	MANE Select	c.1648-38G>T		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1648-38G>T		intron	N/A	NP_001153583.1
	NOS3	NM_001160110.1		c.1648-38G>T		intron	N/A	NP_001153582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1648-38G>T		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000484524.5	TSL:1	c.1648-38G>T		intron	N/A	ENSP00000420215.1
	NOS3	ENST00000467517.1	TSL:1	c.1648-38G>T		intron	N/A	ENSP00000420551.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16059 AN: 151930 Hom.: 979 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.0927 AC: 16634 AN: 179452 AF XY: 0.0955

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.0591

Gnomad ASJ exome AF: 0.0993

Gnomad EAS exome AF: 0.0888

Gnomad FIN exome AF: 0.0956

Gnomad NFE exome AF: 0.0763

Gnomad OTH exome AF: 0.0820

GnomAD4 exome AF: 0.0803 AC: 105632 AN: 1316104 Hom.: 4804 Cov.: 20 AF XY: 0.0826 AC XY: 54069 AN XY: 654494

African (AFR) AF: 0.161 AC: 4904 AN: 30512

American (AMR) AF: 0.0608 AC: 2268 AN: 37314

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 2413 AN: 24634

East Asian (EAS) AF: 0.0948 AC: 3507 AN: 36998

South Asian (SAS) AF: 0.138 AC: 10983 AN: 79352

European-Finnish (FIN) AF: 0.0919 AC: 4601 AN: 50048

Middle Eastern (MID) AF: 0.116 AC: 605 AN: 5204

European-Non Finnish (NFE) AF: 0.0719 AC: 71661 AN: 996930

Other (OTH) AF: 0.0851 AC: 4690 AN: 55112

GnomAD4 genome AF: 0.106 AC: 16058 AN: 152048 Hom.: 977 Cov.: 31 AF XY: 0.107 AC XY: 7969 AN XY: 74328

African (AFR) AF: 0.160 AC: 6654 AN: 41464

American (AMR) AF: 0.0772 AC: 1180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3468

East Asian (EAS) AF: 0.0888 AC: 458 AN: 5156

South Asian (SAS) AF: 0.143 AC: 686 AN: 4814

European-Finnish (FIN) AF: 0.0997 AC: 1056 AN: 10592

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5388 AN: 67954

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0624 Hom.: 86

Bravo AF: 0.105

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.60
PhyloP100		-1.2
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: rs1800782; hg19: chr7-150699250;