chr2-38997210-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Noonan syndrome 4
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
fibromatosis, gingival, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary gingival fibromatosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SOS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.921

AC:

225352

AN:

244650

AF XY:

0.915

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 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

African (AFR)

AF:

0.963

AC:

29519

AN:

30640

American (AMR)

AF:

0.955

AC:

41231

AN:

43174

Ashkenazi Jewish (ASJ)

AF:

0.906

AC:

22660

AN:

25008

East Asian (EAS)

AF:

0.820

AC:

31923

AN:

38930

South Asian (SAS)

AF:

0.849

AC:

69106

AN:

81406

European-Finnish (FIN)

AF:

0.967

AC:

50556

AN:

52278

Middle Eastern (MID)

AF:

0.880

AC:

4802

AN:

5458

European-Non Finnish (NFE)

AF:

0.937

AC:

942868

AN:

1006076

Other (OTH)

AF:

0.918

AC:

51567

AN:

56156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4468

8936

13405

17873

22341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18818

37636

56454

75272

94090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.937

AC:

142727

AN:

152272

Hom.:

67001

Cov.:

AF XY:

0.935

AC XY:

69621

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.962

AC:

39960

AN:

41544

American (AMR)

AF:

0.941

AC:

14392

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

3150

AN:

3472

East Asian (EAS)

AF:

0.815

AC:

4220

AN:

5176

South Asian (SAS)

AF:

0.835

AC:

4028

AN:

4826

European-Finnish (FIN)

AF:

0.972

AC:

10308

AN:

10610

Middle Eastern (MID)

AF:

0.905

AC:

266

AN:

294

European-Non Finnish (NFE)

AF:

0.935

AC:

63627

AN:

68030

Other (OTH)

AF:

0.922

AC:

1950

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

454

908

1362

1816

2270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.934

Hom.:

13975

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

GenomeConnect - CFC International

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Noonan syndrome 4

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.79

(source)

DANN

Benign

0.39

PhyloP100

-0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over