rs2477343

Variant names:

• chr10-27513492-A-G
• rs2477343
• NM_021252.5:c.124+3562A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-27513492-A-G
• chr10-27513492-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAB18	NM_021252.5	c.124+3562A>G		intron_variant	Intron 2 of 6	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.124+3562A>G		intron_variant	Intron 2 of 6	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

African (AFR) AF: 0.207 AC: 8575 AN: 41524

American (AMR) AF: 0.349 AC: 5331 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1056 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4828

European-Finnish (FIN) AF: 0.319 AC: 3369 AN: 10576

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23016 AN: 67982

Other (OTH) AF: 0.311 AC: 657 AN: 2114

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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2477343; hg19: chr10-27802421;