Genetic Variant RAB27A:c.-143+566A>G (chr15-55289150-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_183235.3(RAB27A):c.-143+566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,156 control chromosomes in the GnomAD database, including 5,653 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 0.23 ( 5653 hom., cov: 32)

Exomes 𝑓: 0.080 ( 0 hom. )

Consequence

RAB27A
NM_183235.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.43

Publications

4 publications found

Variant links:

Genes affected

RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

RAB27A Gene-Disease associations (from GenCC):

Griscelli syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

RAB27A links:

ENSG00000276533 (HGNC:):

ENSG00000276533 links:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3 link	c.-143+566A>G		intron_variant	Intron 1 of 6	ENST00000336787.6	NP_899058.1	P51159-1A2RU94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6 link	c.-143+566A>G		intron_variant	Intron 1 of 6	1	NM_183235.3	ENSP00000337761.1		P51159-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34824

AN:

151950

Hom.:

5641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.0795

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0588

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.611

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.229

AC:

34869

AN:

152068

Hom.:

5653

Cov.:

AF XY:

0.231

AC XY:

17186

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.416

AC:

17229

AN:

41454

American (AMR)

AF:

0.244

AC:

3734

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

475

AN:

3470

East Asian (EAS)

AF:

0.548

AC:

2818

AN:

5144

South Asian (SAS)

AF:

0.247

AC:

1188

AN:

4812

European-Finnish (FIN)

AF:

0.124

AC:

1319

AN:

10608

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7544

AN:

67990

Other (OTH)

AF:

0.216

AC:

456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1225

2450

3674

4899

6124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.160

Hom.:

433

Bravo

AF:

0.249

Asia WGS

AF:

0.365

AC:

1270

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.21

(source)

DANN

Benign

0.77

PhyloP100

-4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over