rs4774760

chr15-55297014-T-Achr15-55297014-T-Cchr15-55297014-T-G

Variant summary

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

The ENST00000563262.5(RAB27A):c.-112+17025A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,982 control chromosomes in the GnomAD database, including 6,847 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 0.27 (6847 hom., cov: 32)
• Consequence: RAB27A ENST00000563262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000563262.5	c.-112+17025A>T		intron_variant		3
RAB27A	ENST00000561545.1	n.322-6618A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41410 AN: 151864 Hom.: 6835 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.273 AC: 41456 AN: 151982 Hom.: 6847 Cov.: 32 AF XY: 0.271 AC XY: 20162 AN XY: 74312

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.266

Alfa AF: 0.213 Hom.: 482

Bravo AF: 0.293

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.6
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4774760; hg19: chr15-55589212;