rs8032594

chr15-55265663-G-Achr15-55265663-G-Cchr15-55265663-G-T

Variant summary

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

The NM_183235.3(RAB27A):c.-23+4502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,596 control chromosomes in the GnomAD database, including 25,040 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 0.56 (25040 hom., cov: 30)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.-23+4502C>T		intron_variant		ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+4502C>T		intron_variant		1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84788 AN: 151482 Hom.: 24984 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.560 AC: 84902 AN: 151596 Hom.: 25040 Cov.: 30 AF XY: 0.557 AC XY: 41206 AN XY: 74018

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.533

Alfa AF: 0.520 Hom.: 3684

Bravo AF: 0.584

Asia WGS AF: 0.616 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.2
Dann	Benign	0.44

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: rs8032594; hg19: chr15-55557861;