chr2-38989732-T-C

Position:

• chr2-38989732-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.3347-418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,106 control chromosomes in the GnomAD database, including 61,889 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 0.90 (61889 hom., cov: 33)
• Consequence: SOS1 NM_005633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOS1	NM_005633.4	c.3347-418A>G		intron_variant		ENST00000402219.8	NP_005624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOS1	ENST00000402219.8	c.3347-418A>G		intron_variant		1	NM_005633.4	ENSP00000384675	A1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136714 AN: 151988 Hom.: 61852 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.899 AC: 136805 AN: 152106 Hom.: 61889 Cov.: 33 AF XY: 0.898 AC XY: 66778 AN XY: 74382

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.971

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.898

Alfa AF: 0.935 Hom.: 86268

Bravo AF: 0.892

Asia WGS AF: 0.839 AC: 2875 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.86

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: rs963731; hg19: chr2-39216873;