15-55312954-T-C

Position:

• chr15-55312954-T-C

Variant summary

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

The ENST00000563262.5(RAB27A):​c.-112+1085A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,996 control chromosomes in the GnomAD database, including 6,789 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 (6789 hom., cov: 32)
• Consequence: RAB27A ENST00000563262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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 = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000563262.5	c.-112+1085A>G		intron_variant		3		ENSP00000457595
RAB27A	ENST00000561545.1	n.321+1066A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41651 AN: 151878 Hom.: 6782 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.274 AC: 41686 AN: 151996 Hom.: 6789 Cov.: 32 AF XY: 0.275 AC XY: 20426 AN XY: 74312

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.264

Alfa AF: 0.197 Hom.: 6489

Bravo AF: 0.291

Asia WGS AF: 0.380 AC: 1324 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	0.85
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11636687; hg19: chr15-55605152;