Variant chr2-38997473-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005633.4(SOS1):c.2792-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 37 hom. )

Consequence

SOS1
NM_005633.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.560

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=-0.84).

BP6

Variant 2-38997473-A-G is Benign according to our data. Variant chr2-38997473-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00921 (385/41806) while in subpopulation NFE AF= 0.0283 (255/9014). AF 95% confidence interval is 0.0254. There are 3 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4 linkuse as main transcript	c.2792-48T>C		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.2792-48T>C		intron_variant		1	NM_005633.4	ENSP00000384675	A1	Q07889-1

Frequencies

GnomAD3 genomes

AF:

0.00920

AC:

384

AN:

41738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.00845

Gnomad MID

AF:

0.0294

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0207

AC:

909

AN:

43884

Hom.:

AF XY:

0.0238

AC XY:

573

AN XY:

24052

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0325

Gnomad FIN exome

AF:

0.00922

Gnomad NFE exome

AF:

0.0332

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.00357

AC:

4297

AN:

1204194

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

2387

AN XY:

610756

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00805

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00892

Gnomad4 FIN exome

AF:

0.000494

Gnomad4 NFE exome

AF:

0.00339

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00921

AC:

385

AN:

41806

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

178

AN XY:

20276

show subpopulations

Gnomad4 AFR

AF:

0.000888

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.00845

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0124

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00260

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.8

DANN

Benign

0.78

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