15-55212141-A-G

Position:

• chr15-55212141-A-G

Variant summary

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

The NM_183235.3(RAB27A):​c.468-6436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,134 control chromosomes in the GnomAD database, including 982 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 0.11 (982 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.468-6436T>C		intron_variant		ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.468-6436T>C		intron_variant		1	NM_183235.3	ENSP00000337761	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16928 AN: 152016 Hom.: 981 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16937 AN: 152134 Hom.: 982 Cov.: 31 AF XY: 0.110 AC XY: 8219 AN XY: 74384

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0831

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.104

Alfa AF: 0.112 Hom.: 137

Bravo AF: 0.109

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.44

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: rs9920165; hg19: chr15-55504339;