Genetic Variant NM_021252.5:c.187-55T>A (chr10-27532452-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.449

Publications

4 publications found

Variant links:

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

RAB18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAB18	NM_021252.5 link	c.187-55T>A		intron_variant	Intron 3 of 6	ENST00000356940.11	NP_067075.1	Q9NP72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11 link	c.187-55T>A		intron_variant	Intron 3 of 6	1	NM_021252.5	ENSP00000349415.7		Q9NP72-1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3535

AN:

152034

Hom.:

317

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

26272

American (AMR)

AF:

0.0502

AC:

2178

AN:

43420

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

375

AN:

23860

East Asian (EAS)

AF:

0.378

AC:

14244

AN:

37672

South Asian (SAS)

AF:

0.116

AC:

9047

AN:

77806

European-Finnish (FIN)

AF:

0.0316

AC:

1580

AN:

50002

Middle Eastern (MID)

AF:

0.0203

AC:

AN:

3686

European-Non Finnish (NFE)

AF:

0.00242

AC:

1965

AN:

812676

Other (OTH)

AF:

0.0310

AC:

1517

AN:

48944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1160

2320

3479

4639

5799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3530

AN:

152152

Hom.:

314

Cov.:

AF XY:

0.0283

AC XY:

2108

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00277

AC:

115

AN:

41554

American (AMR)

AF:

0.0338

AC:

517

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3468

East Asian (EAS)

AF:

0.304

AC:

1570

AN:

5172

South Asian (SAS)

AF:

0.141

AC:

681

AN:

4826

European-Finnish (FIN)

AF:

0.0318

AC:

337

AN:

10596

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00306

AC:

208

AN:

67936

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

Hom.:

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

(source)

DANN

Benign

0.74

PhyloP100

-0.45

PromoterAI

0.0096

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over