10-27526736-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021252.5(RAB18):c.125-92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,520,372 control chromosomes in the GnomAD database, including 77,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6505 hom., cov: 31)
  • Exomes 𝑓: 0.32 (71410 hom.)
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.495

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-27526736-A-G is Benign according to our data. Variant chr10-27526736-A-G is described in ClinVar as [Benign]. Clinvar id is 668606.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB18	NM_021252.5	c.125-92A>G		intron_variant		ENST00000356940.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB18	ENST00000356940.11	c.125-92A>G		intron_variant		1	NM_021252.5	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42888 AN: 151854 Hom.: 6499 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.319 AC: 435997 AN: 1368400 Hom.: 71410 AF XY: 0.316 AC XY: 216423 AN XY: 684540

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.282 AC: 42924 AN: 151972 Hom.: 6505 Cov.: 31 AF XY: 0.280 AC XY: 20840 AN XY: 74310

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.304

Alfa AF: 0.320 Hom.: 10684

Bravo AF: 0.282

Asia WGS AF: 0.233 AC: 814 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.88
Dann	Benign	0.53

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: rs2642273; hg19: chr10-27815665; COSMIC: COSV63614052;