rs12901464

chr15-55299714-A-Gchr15-55299714-A-T

Variant summary

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

The ENST00000563262.5(RAB27A):c.-112+14325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,288 control chromosomes in the GnomAD database, including 226 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 0.043 (226 hom., cov: 31)
• Consequence: RAB27A ENST00000563262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0523 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+14325T>C		intron_variant		3
RAB27A	ENST00000561545.1	n.322-9318T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6592 AN: 152170 Hom.: 226 Cov.: 31

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00922

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0427

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

GnomAD4 genome AF: 0.0433 AC: 6594 AN: 152288 Hom.: 226 Cov.: 31 AF XY: 0.0456 AC XY: 3395 AN XY: 74472

Gnomad4 AFR AF: 0.00839

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00924

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0423

Alfa AF: 0.0481 Hom.: 27

Bravo AF: 0.0374

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.8
Dann	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12901464; hg19: chr15-55591912;