15-55257363-G-C

Variant names:

• chr15-55257363-G-C
• rs11630859
• NM_183235.3:c.-23+12802C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.-23+12802C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,990 control chromosomes in the GnomAD database, including 8,918 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 0.33 (8918 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	NM_183235.3	MANE Select	c.-23+12802C>G		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.-112+12802C>G		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-23+12802C>G		intron	N/A	NP_001425901.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.-23+12802C>G		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.-23+12802C>G		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.-112+12802C>G		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49591 AN: 151872 Hom.: 8920 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49601 AN: 151990 Hom.: 8918 Cov.: 31 AF XY: 0.327 AC XY: 24259 AN XY: 74296

African (AFR) AF: 0.252 AC: 10450 AN: 41470

American (AMR) AF: 0.352 AC: 5378 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3466

East Asian (EAS) AF: 0.791 AC: 4066 AN: 5142

South Asian (SAS) AF: 0.454 AC: 2183 AN: 4812

European-Finnish (FIN) AF: 0.293 AC: 3099 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22102 AN: 67956

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.303 Hom.: 880

Bravo AF: 0.329

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11630859; hg19: chr15-55549561;