Variant rs1454223 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.2964+43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 1,491,398 control chromosomes in the GnomAD database, including 645,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67001 hom., cov: 33)

Exomes 𝑓: 0.93 ( 578814 hom. )

Consequence

SOS1
NM_005633.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.745

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-38997210-G-T is Benign according to our data. Variant chr2-38997210-G-T is described in ClinVar as [Benign]. Clinvar id is 259848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOS1	NM_005633.4 link	c.2964+43C>A		intron_variant	Intron 18 of 22	ENST00000402219.8	NP_005624.2	Q07889-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOS1	ENST00000402219.8 link	c.2964+43C>A		intron_variant	Intron 18 of 22	1	NM_005633.4	ENSP00000384675.2		Q07889-1

Frequencies

GnomAD3 genomes

AF:

0.937

AC:

142607

AN:

152154

Hom.:

66941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.962

Gnomad AMI

AF:

0.906

Gnomad AMR

AF:

0.941

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.972

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.935

Gnomad OTH

AF:

0.923

GnomAD3 exomes

AF:

0.921

AC:

225352

AN:

244650

Hom.:

104132

AF XY:

0.915

AC XY:

121474

AN XY:

132686

show subpopulations

Gnomad AFR exome

AF:

0.963

Gnomad AMR exome

AF:

0.958

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

0.824

Gnomad SAS exome

AF:

0.843

Gnomad FIN exome

AF:

0.968

Gnomad NFE exome

AF:

0.934

Gnomad OTH exome

AF:

0.911

GnomAD4 exome

AF:

0.929

AC:

1244232

AN:

1339126

Hom.:

578814

Cov.:

AF XY:

0.926

AC XY:

622513

AN XY:

672056

show subpopulations

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.955

Gnomad4 ASJ exome

AF:

0.906

Gnomad4 EAS exome

AF:

0.820

Gnomad4 SAS exome

AF:

0.849

Gnomad4 FIN exome

AF:

0.967

Gnomad4 NFE exome

AF:

0.937

Gnomad4 OTH exome

AF:

0.918

GnomAD4 genome

AF:

0.937

AC:

142727

AN:

152272

Hom.:

67001

Cov.:

AF XY:

0.935

AC XY:

69621

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.962

Gnomad4 AMR

AF:

0.941

Gnomad4 ASJ

AF:

0.907

Gnomad4 EAS

AF:

0.815

Gnomad4 SAS

AF:

0.835

Gnomad4 FIN

AF:

0.972

Gnomad4 NFE

AF:

0.935

Gnomad4 OTH

AF:

0.922

Alfa

AF:

0.934

Hom.:

13632

Bravo

AF:

0.937

Asia WGS

AF:

0.847

AC:

2940

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:2Other: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	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.79

DANN

Benign

0.39

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