rs2168043

Positions:

• chr2-39104952-A-C
• chr2-39104952-A-T

Variant summary

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

The NM_005633.4(SOS1):​c.87+15384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,094 control chromosomes in the GnomAD database, including 41,438 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 0.71 (41438 hom., cov: 33)
• Consequence: SOS1 NM_005633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOS1	NM_005633.4	c.87+15384T>G		intron_variant		ENST00000402219.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOS1	ENST00000402219.8	c.87+15384T>G		intron_variant		1	NM_005633.4	A1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107606 AN: 151976 Hom.: 41421 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.708 AC: 107653 AN: 152094 Hom.: 41438 Cov.: 33 AF XY: 0.711 AC XY: 52824 AN XY: 74334

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.727

Alfa AF: 0.792 Hom.: 20436

Bravo AF: 0.686

Asia WGS AF: 0.777 AC: 2702 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.54

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: rs2168043; hg19: chr2-39332093;