15-55242144-C-T

Position:

• chr15-55242144-C-T

Variant summary

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

The NM_183235.3(RAB27A):​c.-22-7188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,846 control chromosomes in the GnomAD database, including 21,163 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 0.52 (21163 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-22-7188G>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.-22-7188G>A		intron_variant		1	NM_183235.3	ENSP00000337761	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78921 AN: 151728 Hom.: 21125 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.520 AC: 79014 AN: 151846 Hom.: 21163 Cov.: 31 AF XY: 0.519 AC XY: 38535 AN XY: 74188

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.528

Alfa AF: 0.488 Hom.: 11182

Bravo AF: 0.538

Asia WGS AF: 0.603 AC: 2097 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.33

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: rs2444043; hg19: chr15-55534342;