NM_183235.3:c.-143+566A>G

Variant names:

• chr15-55289150-T-C
• rs2305424
• NM_183235.3:c.-143+566A>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.-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.43
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ENSG00000276533 (HGNC:):

ACMG classification

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.

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.-143+566A>G		intron	N/A	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.-231-18866A>G		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-143+302A>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.-143+566A>G		intron	N/A	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000697642.1		c.-23+566A>G		intron	N/A	ENSP00000513368.1	P51159-1
	RAB27A	ENST00000697643.1		c.-232+566A>G		intron	N/A	ENSP00000513369.1	P51159-1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34824 AN: 151950 Hom.: 5641 Cov.: 32

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: 7 AN: 88 Hom.: 0 Cov.: 0 AF XY: 0.0588 AC XY: 4 AN XY: 68

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 6 AN: 72

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.229 AC: 34869 AN: 152068 Hom.: 5653 Cov.: 32 AF XY: 0.231 AC XY: 17186 AN XY: 74322

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: 47 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7544 AN: 67990

Other (OTH) AF: 0.216 AC: 456 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.21
DANN	Benign	0.77
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2305424; hg19: chr15-55581348;