7-150996342-C-G

Variant names:

• chr7-150996342-C-G
• rs11974098
• NM_000603.5:c.271-62C>G

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.271-62C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 824,400 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (53 hom., cov: 7)
  • Exomes 𝑓: 0.0046 (186 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377
• Publications: 0 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=-0.9).
• BP6: Variant 7-150996342-C-G is Benign according to our data. Variant chr7-150996342-C-G is described in ClinVar as Benign. ClinVar VariationId is 1269294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.271-62C>G		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.271-62C>G		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.271-62C>G		intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.271-62C>G		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.271-62C>G		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.271-62C>G		intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 503 AN: 45582 Hom.: 52 Cov.: 7

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00375

Gnomad ASJ AF: 0.00242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00420

Gnomad FIN AF: 0.000557

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.00456 AC: 3552 AN: 778814 Hom.: 186 AF XY: 0.00464 AC XY: 1842 AN XY: 396788

African (AFR) AF: 0.0769 AC: 1343 AN: 17460

American (AMR) AF: 0.00580 AC: 148 AN: 25528

Ashkenazi Jewish (ASJ) AF: 0.00745 AC: 130 AN: 17442

East Asian (EAS) AF: 0.00 AC: 0 AN: 25662

South Asian (SAS) AF: 0.0111 AC: 652 AN: 58934

European-Finnish (FIN) AF: 0.00141 AC: 56 AN: 39804

Middle Eastern (MID) AF: 0.0128 AC: 36 AN: 2810

European-Non Finnish (NFE) AF: 0.00168 AC: 938 AN: 556820

Other (OTH) AF: 0.00725 AC: 249 AN: 34354

GnomAD4 genome AF: 0.0111 AC: 506 AN: 45586 Hom.: 53 Cov.: 7 AF XY: 0.0120 AC XY: 257 AN XY: 21470

African (AFR) AF: 0.0538 AC: 446 AN: 8292

American (AMR) AF: 0.00375 AC: 14 AN: 3732

Ashkenazi Jewish (ASJ) AF: 0.00242 AC: 3 AN: 1242

East Asian (EAS) AF: 0.00 AC: 0 AN: 2420

South Asian (SAS) AF: 0.00282 AC: 4 AN: 1416

European-Finnish (FIN) AF: 0.000557 AC: 2 AN: 3588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.00142 AC: 34 AN: 23976

Other (OTH) AF: 0.00560 AC: 3 AN: 536

Alfa AF: 0.0180 Hom.: 10

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		-0.38
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: rs11974098; hg19: chr7-150693430;