rs3765133

chr10-27532452-T-Achr10-27532452-T-G

Variant summary

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

The NM_021252.5(RAB18):c.187-55T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,276,490 control chromosomes in the GnomAD database, including 3,993 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 0.023 (314 hom., cov: 32)
  • Exomes 𝑓: 0.028 (3679 hom.)
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB18	NM_021252.5	c.187-55T>A		intron_variant		ENST00000356940.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB18	ENST00000356940.11	c.187-55T>A		intron_variant		1	NM_021252.5	P1

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3535 AN: 152034 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0276 AC: 31025 AN: 1124338 Hom.: 3679 AF XY: 0.0302 AC XY: 17375 AN XY: 574978

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.0502

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0316

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0232 AC: 3530 AN: 152152 Hom.: 314 Cov.: 32 AF XY: 0.0283 AC XY: 2108 AN XY: 74394

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0112 Hom.: 8

Bravo AF: 0.0228

Asia WGS AF: 0.195 AC: 673 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Benign	0.74

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: rs3765133; hg19: chr10-27821381; COSMIC: COSV63613255;