Variant chr7-150996397-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000603.5(NOS3):c.271-7G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,226,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

NOS3
NM_000603.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001679

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.271

Variant links:

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]

NOS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-150996397-G-T is Benign according to our data. Variant chr7-150996397-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 715805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NOS3	NM_000603.5 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000297494.8
NOS3	NM_001160109.2 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NOS3	NM_001160110.1 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
NOS3	NM_001160111.1 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_000603.5	P1	P29474-1
NOS3	ENST00000467517.1 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1			P29474-3
NOS3	ENST00000484524.5 linkuse as main transcript	c.271-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1			P29474-2
NOS3	ENST00000461406.5 linkuse as main transcript	c.-37+1083G>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

70706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000260

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000660

AC:

AN:

151456

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1156040

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

567206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000353

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000173

Gnomad4 OTH exome

AF:

0.0000478

GnomAD4 genome

AF:

0.0000141

AC:

AN:

70706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31750

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000260

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.32

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over