10-27504701-C-G

Variant names:

• chr10-27504701-C-G
• rs146545118
• NM_021252.5:c.68+264C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021252.5(RAB18):​c.68+264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Warburg micro syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Warburg micro syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

LOC124902399 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB18	NM_021252.5	c.68+264C>G		intron_variant	Intron 1 of 6	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.68+264C>G		intron_variant	Intron 1 of 6	1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000568 AC: 1 AN: 175972 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000184 AC: 1 AN: 544160 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 296388

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15624

American (AMR) AF: 0.00 AC: 0 AN: 36684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19102

East Asian (EAS) AF: 0.00 AC: 0 AN: 29974

South Asian (SAS) AF: 0.00 AC: 0 AN: 63934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3186

European-Non Finnish (NFE) AF: 0.00000330 AC: 1 AN: 302986

Other (OTH) AF: 0.00 AC: 0 AN: 28780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.72
PromoterAI		0.0018	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146545118; hg19: chr10-27793630;