Variant 2-38997474-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000402219.8(SOS1):c.2792-50_2792-49insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54883 hom., cov: 0)

Exomes 𝑓: 0.92 ( 476439 hom. )

Consequence

SOS1
ENST00000402219.8 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.245

Variant links:

Genes affected

SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

SOS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-38997474-G-GT is Benign according to our data. Variant chr2-38997474-G-GT is described in ClinVar as [Benign]. Clinvar id is 259847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4 linkuse as main transcript	c.2792-50_2792-49insA		intron_variant		ENST00000402219.8	NP_005624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOS1	ENST00000402219.8 linkuse as main transcript	c.2792-50_2792-49insA		intron_variant		1	NM_005633.4	ENSP00000384675	A1	Q07889-1

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127227

AN:

151860

Hom.:

54857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.616

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.903

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.935

Gnomad OTH

AF:

0.854

GnomAD3 exomes

AF:

0.892

AC:

208894

AN:

234068

Hom.:

94165

AF XY:

0.893

AC XY:

114152

AN XY:

127794

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.938

Gnomad ASJ exome

AF:

0.901

Gnomad EAS exome

AF:

0.817

Gnomad SAS exome

AF:

0.841

Gnomad FIN exome

AF:

0.967

Gnomad NFE exome

AF:

0.933

Gnomad OTH exome

AF:

0.894

GnomAD4 exome

AF:

0.915

AC:

1034668

AN:

1130670

Hom.:

476439

Cov.:

AF XY:

0.914

AC XY:

528189

AN XY:

578116

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.932

Gnomad4 ASJ exome

AF:

0.902

Gnomad4 EAS exome

AF:

0.807

Gnomad4 SAS exome

AF:

0.845

Gnomad4 FIN exome

AF:

0.966

Gnomad4 NFE exome

AF:

0.936

Gnomad4 OTH exome

AF:

0.893

GnomAD4 genome

AF:

0.838

AC:

127299

AN:

151978

Hom.:

54883

Cov.:

AF XY:

0.838

AC XY:

62293

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.904

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.971

Gnomad4 NFE

AF:

0.935

Gnomad4 OTH

AF:

0.855

Alfa

AF:

0.888

Hom.:

7073

Bravo

AF:

0.819

Asia WGS

AF:

0.819

AC:

2840

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	phenotyping only	GenomeConnect - CFC International	-	Variant interpreted as Benign and reported on 04-30-2009 by Lab or GTR ID 239772. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Noonan syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Fibromatosis, gingival, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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