Genetic Variant RAB27A:c.*2007G>A (chr15-55203500-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_183235.3(RAB27A):c.*2007G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 148,284 control chromosomes in the GnomAD database, including 6,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6849 hom., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB27A
NM_183235.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.776

Publications

3 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

RAB27A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 15-55203500-C-T is Benign according to our data. Variant chr15-55203500-C-T is described in ClinVar as Benign. ClinVar VariationId is 316611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB27A	NM_183235.3	MANE Select	c.*2007G>A	3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
RAB27A	NM_001438970.1		c.*2007G>A	3_prime_UTR	Exon 8 of 8	NP_001425899.1
RAB27A	NM_001438972.1		c.*2007G>A	3_prime_UTR	Exon 7 of 7	NP_001425901.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.*2007G>A	3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
RAB27A	ENST00000396307.6	TSL:1	c.*2007G>A	3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
RAB27A	ENST00000899597.1		c.*2007G>A	3_prime_UTR	Exon 7 of 7	ENSP00000569656.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

39258

AN:

148188

Hom.:

6831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.225

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.265

AC:

39310

AN:

148284

Hom.:

6849

Cov.:

AF XY:

0.259

AC XY:

18669

AN XY:

72212

show subpopulations

African (AFR)

AF:

0.494

AC:

19577

AN:

39662

American (AMR)

AF:

0.158

AC:

2351

AN:

14910

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

537

AN:

3458

East Asian (EAS)

AF:

0.117

AC:

597

AN:

5088

South Asian (SAS)

AF:

0.222

AC:

1040

AN:

4692

European-Finnish (FIN)

AF:

0.151

AC:

1494

AN:

9884

Middle Eastern (MID)

AF:

0.179

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.190

AC:

12779

AN:

67368

Other (OTH)

AF:

0.223

AC:

455

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

1214

2428

3641

4855

6069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.237

Hom.:

700

Bravo

AF:

0.277

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Griscelli syndrome type 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.0

(source)

DANN

Benign

0.51

PhyloP100

-0.78

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over