rs8032859

Positions:

• chr15-55258557-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.-23+11608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,102 control chromosomes in the GnomAD database, including 47,148 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 0.78 (47148 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-23+11608C>T		intron_variant		ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+11608C>T		intron_variant		1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118171 AN: 151986 Hom.: 47155 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.777 AC: 118196 AN: 152102 Hom.: 47148 Cov.: 31 AF XY: 0.778 AC XY: 57872 AN XY: 74376

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.818

Alfa AF: 0.844 Hom.: 74760

Bravo AF: 0.761

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs8032859; hg19: chr15-55550755;