chr15-55240013-G-T

Position:

• chr15-55240013-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.-22-5057C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,824 control chromosomes in the GnomAD database, including 10,194 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 0.35 (10194 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

RAB27A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-22-5057C>A		intron_variant		ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-22-5057C>A		intron_variant		1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52649 AN: 151704 Hom.: 10195 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.347 AC: 52664 AN: 151824 Hom.: 10194 Cov.: 32 AF XY: 0.346 AC XY: 25703 AN XY: 74210

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.379

Alfa AF: 0.380 Hom.: 15065

Bravo AF: 0.349

Asia WGS AF: 0.538 AC: 1868 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.028
DANN	Benign	0.49

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: rs2444039; hg19: chr15-55532211;