rs16976228

Variant names:

• chr15-55250935-T-C
• rs16976228
• NM_183235.3:c.-22-15979A>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.-22-15979A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,086 control chromosomes in the GnomAD database, including 1,122 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 0.066 (1122 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	NM_183235.3	MANE Select	c.-22-15979A>G		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.-111-12444A>G		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-22-15979A>G		intron	N/A	NP_001425901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.-22-15979A>G		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.-22-15979A>G		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.-111-12444A>G		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10052 AN: 151968 Hom.: 1116 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0663 AC: 10083 AN: 152086 Hom.: 1122 Cov.: 32 AF XY: 0.0632 AC XY: 4696 AN XY: 74342

African (AFR) AF: 0.230 AC: 9516 AN: 41446

American (AMR) AF: 0.0248 AC: 379 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10572

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68004

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0245 Hom.: 405

Bravo AF: 0.0754

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.77
PhyloP100		-1.8
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: rs16976228; hg19: chr15-55543133;