Genetic Variant NM_021252.5:c.68+264C>A (chr10-27504701-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021252.5(RAB18):c.68+264C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 696,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

RAB18
NM_021252.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

0 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: Labcorp Genetics (formerly Invitae), G2P
Warburg micro syndrome
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

RAB18 links:

LOC124902399 (HGNC:):

LOC124902399 links:

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ACMG classification

Classification was made for transcript

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB18	NM_021252.5	MANE Select	c.68+264C>A	intron	N/A	NP_067075.1	Q9NP72-1
RAB18	NM_001256410.2		c.68+264C>A	intron	N/A	NP_001243339.1	Q9NP72-2
RAB18	NM_001256411.2		c.68+264C>A	intron	N/A	NP_001243340.1	B7Z4P9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB18	ENST00000356940.11	TSL:1 MANE Select	c.68+264C>A	intron	N/A	ENSP00000349415.7	Q9NP72-1
RAB18	ENST00000621805.6	TSL:1	c.68+264C>A	intron	N/A	ENSP00000478479.1	Q9NP72-2
RAB18	ENST00000423465.2	TSL:5	c.-429C>A	5_prime_UTR	Exon 1 of 7	ENSP00000407872.2	H0Y6T8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

544160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

296388

show subpopulations

African (AFR)

AF:

0.0000640

AC:

AN:

15624

American (AMR)

AF:

0.00

AC:

AN:

36684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19102

East Asian (EAS)

AF:

0.00

AC:

AN:

29974

South Asian (SAS)

AF:

0.00

AC:

AN:

63934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

302986

Other (OTH)

AF:

0.00

AC:

AN:

28780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

(source)

DANN

Benign

0.64

PhyloP100

-0.72

PromoterAI

-0.042

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over