rs2477343

Positions:

• chr10-27513492-A-G

Variant summary

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

The NM_021252.5(RAB18):​c.124+3562A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,148 control chromosomes in the GnomAD database, including 6,793 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 0.29 (6793 hom., cov: 31)
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482

Genes affected

RAB18 (HGNC:14244): (RAB18, member RAS oncogene family) The protein encoded by this gene is a member of a family of Ras-related small GTPases that regulate membrane trafficking in organelles and transport vesicles. Knockdown studies is zebrafish suggest that this protein may have a role in eye and brain development. Mutations in this gene are associated with Warburg micro syndrome type 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

RAB18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB18	NM_021252.5	c.124+3562A>G		intron_variant		ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.124+3562A>G		intron_variant		1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44298 AN: 152032 Hom.: 6783 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.291 AC: 44347 AN: 152148 Hom.: 6793 Cov.: 31 AF XY: 0.289 AC XY: 21519 AN XY: 74368

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.311

Alfa AF: 0.319 Hom.: 968

Bravo AF: 0.292

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.85

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: rs2477343; hg19: chr10-27802421;