10-27504701-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021252.5(RAB18):c.68+264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 696,440 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (38 hom.)
• Consequence: RAB18 NM_021252.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719

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]

LOC124902399 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-27504701-C-T is Benign according to our data. Variant chr10-27504701-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00617 (3357/544136) while in subpopulation SAS AF= 0.0166 (1061/63930). AF 95% confidence interval is 0.0158. There are 38 homozygotes in gnomad4_exome. There are 1962 alleles in male gnomad4_exome subpopulation. Median coverage is 4. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB18	NM_021252.5	c.68+264C>T		intron_variant		ENST00000356940.11
LOC124902399	XR_007062097.1	n.257C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB18	ENST00000356940.11	c.68+264C>T		intron_variant		1	NM_021252.5	P1

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 579 AN: 152186 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00609 AC: 1072 AN: 175972 Hom.: 13 AF XY: 0.00690 AC XY: 665 AN XY: 96418

Gnomad AFR exome AF: 0.000441

Gnomad AMR exome AF: 0.000931

Gnomad ASJ exome AF: 0.000342

Gnomad EAS exome AF: 0.0000756

Gnomad SAS exome AF: 0.0166

Gnomad FIN exome AF: 0.0230

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00399

GnomAD4 exome AF: 0.00617 AC: 3357 AN: 544136 Hom.: 38 Cov.: 4 AF XY: 0.00662 AC XY: 1962 AN XY: 296376

Gnomad4 AFR exome AF: 0.000640

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.000157

Gnomad4 EAS exome AF: 0.000234

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0247

Gnomad4 NFE exome AF: 0.00326

Gnomad4 OTH exome AF: 0.00455

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152304 Hom.: 7 Cov.: 33 AF XY: 0.00458 AC XY: 341 AN XY: 74472

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00203 Hom.: 0

Bravo AF: 0.00210

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 27, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.8
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs146545118; hg19: chr10-27793630;