rs2888586

Positions:

• chr2-39020148-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005633.4(SOS1):​c.1858+2422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,376 control chromosomes in the GnomAD database, including 19,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (19686 hom., cov: 31)
• Consequence: SOS1 NM_005633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOS1	NM_005633.4	c.1858+2422A>G		intron_variant		ENST00000402219.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOS1	ENST00000402219.8	c.1858+2422A>G		intron_variant		1	NM_005633.4	A1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70470 AN: 151258 Hom.: 19675 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.466 AC: 70487 AN: 151376 Hom.: 19686 Cov.: 31 AF XY: 0.470 AC XY: 34755 AN XY: 73996

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.508

Alfa AF: 0.543 Hom.: 12778

Bravo AF: 0.452

Asia WGS AF: 0.598 AC: 2073 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs2888586; hg19: chr2-39247289;