15-55253508-G-C

Variant names:

• chr15-55253508-G-C
• rs12910930
• NM_183235.3:c.-23+16657C>G

Variant summary

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

The NM_183235.3(RAB27A):​c.-23+16657C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,730 control chromosomes in the GnomAD database, including 19,183 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 0.50 (19183 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-23+16657C>G		intron_variant	Intron 2 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+16657C>G		intron_variant	Intron 2 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75141 AN: 151610 Hom.: 19169 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.496 AC: 75192 AN: 151730 Hom.: 19183 Cov.: 31 AF XY: 0.497 AC XY: 36867 AN XY: 74124

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.483

Alfa AF: 0.425 Hom.: 1312

Bravo AF: 0.477

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.76
DANN	Benign	0.17

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: rs12910930; hg19: chr15-55545706;