rs17238192

Variant names:

• chr15-55222748-C-T
• rs17238192
• NM_183235.3:c.467+1141G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.467+1141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,994 control chromosomes in the GnomAD database, including 2,630 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 0.17 (2630 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Griscelli syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.467+1141G>A		intron_variant	Intron 6 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.467+1141G>A		intron_variant	Intron 6 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26273 AN: 151876 Hom.: 2623 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.173 AC: 26320 AN: 151994 Hom.: 2630 Cov.: 32 AF XY: 0.173 AC XY: 12864 AN XY: 74324

African (AFR) AF: 0.256 AC: 10606 AN: 41384

American (AMR) AF: 0.233 AC: 3563 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5176

South Asian (SAS) AF: 0.0901 AC: 435 AN: 4826

European-Finnish (FIN) AF: 0.143 AC: 1509 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8841 AN: 67978

Other (OTH) AF: 0.153 AC: 322 AN: 2108

Alfa AF: 0.143 Hom.: 2586

Bravo AF: 0.186

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17238192; hg19: chr15-55514946;