Variant 2-39054589-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005633.4(SOS1):c.720+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,272,808 control chromosomes in the GnomAD database, including 530,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 65075 hom., cov: 32)

Exomes 𝑓: 0.91 ( 465733 hom. )

Consequence

SOS1
NM_005633.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.808

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-39054589-G-C is Benign according to our data. Variant chr2-39054589-G-C is described in ClinVar as [Benign]. Clinvar id is 180179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOS1	NM_005633.4 linkuse as main transcript	c.720+25C>G		intron_variant		ENST00000402219.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOS1	ENST00000402219.8 linkuse as main transcript	c.720+25C>G		intron_variant		1	NM_005633.4	A1	Q07889-1

Frequencies

GnomAD3 genomes

AF:

0.924

AC:

140519

AN:

152132

Hom.:

65015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.906

Gnomad AMR

AF:

0.904

Gnomad ASJ

AF:

0.891

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.913

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.919

Gnomad OTH

AF:

0.910

GnomAD3 exomes

AF:

0.902

AC:

222952

AN:

247126

Hom.:

100892

AF XY:

0.897

AC XY:

119992

AN XY:

133774

show subpopulations

Gnomad AFR exome

AF:

0.971

Gnomad AMR exome

AF:

0.931

Gnomad ASJ exome

AF:

0.887

Gnomad EAS exome

AF:

0.828

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.906

Gnomad NFE exome

AF:

0.916

Gnomad OTH exome

AF:

0.890

GnomAD4 exome

AF:

0.911

AC:

1020792

AN:

1120560

Hom.:

465733

Cov.:

AF XY:

0.908

AC XY:

520677

AN XY:

573434

show subpopulations

Gnomad4 AFR exome

AF:

0.973

Gnomad4 AMR exome

AF:

0.927

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.839

Gnomad4 FIN exome

AF:

0.910

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.901

GnomAD4 genome

AF:

0.924

AC:

140638

AN:

152248

Hom.:

65075

Cov.:

AF XY:

0.920

AC XY:

68446

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.971

Gnomad4 AMR

AF:

0.904

Gnomad4 ASJ

AF:

0.891

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.827

Gnomad4 FIN

AF:

0.913

Gnomad4 NFE

AF:

0.919

Gnomad4 OTH

AF:

0.910

Alfa

AF:

0.917

Hom.:

11292

Bravo

AF:

0.927

Asia WGS

AF:

0.843

AC:

2927

AN:

3468

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
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. -

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

Jul 15, 2021

- -

Noonan syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Mar 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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