rs4261468

Variant names:

• chr15-55263404-A-G
• rs4261468
• NM_183235.3:c.-23+6761T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-55263404-A-G
• chr15-55263404-A-T

Variant summary

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

The NM_183235.3(RAB27A):​c.-23+6761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,988 control chromosomes in the GnomAD database, including 9,910 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 0.33 (9910 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-23+6761T>C		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+6761T>C		intron_variant	Intron 2 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50753 AN: 151870 Hom.: 9889 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.334 AC: 50810 AN: 151988 Hom.: 9910 Cov.: 32 AF XY: 0.334 AC XY: 24784 AN XY: 74312

African (AFR) AF: 0.532 AC: 22037 AN: 41388

American (AMR) AF: 0.308 AC: 4693 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3020 AN: 5170

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4826

European-Finnish (FIN) AF: 0.212 AC: 2245 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15477 AN: 67984

Other (OTH) AF: 0.315 AC: 663 AN: 2106

Alfa AF: 0.266 Hom.: 18910

Bravo AF: 0.353

Asia WGS AF: 0.404 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-0.10
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: rs4261468; hg19: chr15-55555602;