NM_183235.3:c.-22-5057C>A

Variant names:

• chr15-55240013-G-T
• rs2444039
• NM_183235.3:c.-22-5057C>A

Variant summary

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

The NM_183235.3(RAB27A):​c.-22-5057C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,824 control chromosomes in the GnomAD database, including 10,194 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 0.35 (10194 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 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.-22-5057C>A		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.-111-1522C>A		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-22-5057C>A		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.-22-5057C>A		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.-22-5057C>A		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.-111-1522C>A		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52649 AN: 151704 Hom.: 10195 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.347 AC: 52664 AN: 151824 Hom.: 10194 Cov.: 32 AF XY: 0.346 AC XY: 25703 AN XY: 74210

African (AFR) AF: 0.206 AC: 8528 AN: 41426

American (AMR) AF: 0.413 AC: 6290 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1680 AN: 3458

East Asian (EAS) AF: 0.723 AC: 3722 AN: 5150

South Asian (SAS) AF: 0.463 AC: 2223 AN: 4804

European-Finnish (FIN) AF: 0.322 AC: 3397 AN: 10534

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25597 AN: 67930

Other (OTH) AF: 0.379 AC: 798 AN: 2106

Alfa AF: 0.373 Hom.: 34783

Bravo AF: 0.349

Asia WGS AF: 0.538 AC: 1868 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.028
DANN	Benign	0.49
PhyloP100		-1.7
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: rs2444039; hg19: chr15-55532211;