rs11630859

chr15-55257363-G-Cchr15-55257363-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+12802C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,990 control chromosomes in the GnomAD database, including 8,918 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 0.33 (8918 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.-23+12802C>G		intron_variant		ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+12802C>G		intron_variant		1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49591 AN: 151872 Hom.: 8920 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.326 AC: 49601 AN: 151990 Hom.: 8918 Cov.: 31 AF XY: 0.327 AC XY: 24259 AN XY: 74296

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.346

Alfa AF: 0.303 Hom.: 880

Bravo AF: 0.329

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.4
Dann	Benign	0.72

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: rs11630859; hg19: chr15-55549561;