NM_183235.3:c.-23+11608C>T

Variant names:

• chr15-55258557-G-A
• rs8032859
• NM_183235.3:c.-23+11608C>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+11608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,102 control chromosomes in the GnomAD database, including 47,148 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 0.78 (47148 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-23+11608C>T		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+11608C>T		intron_variant	Intron 2 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118171 AN: 151986 Hom.: 47155 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.777 AC: 118196 AN: 152102 Hom.: 47148 Cov.: 31 AF XY: 0.778 AC XY: 57872 AN XY: 74376

African (AFR) AF: 0.588 AC: 24374 AN: 41446

American (AMR) AF: 0.749 AC: 11440 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4929 AN: 5178

South Asian (SAS) AF: 0.914 AC: 4413 AN: 4826

European-Finnish (FIN) AF: 0.834 AC: 8831 AN: 10590

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58550 AN: 68004

Other (OTH) AF: 0.818 AC: 1727 AN: 2110

Alfa AF: 0.834 Hom.: 92454

Bravo AF: 0.761

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.71
PhyloP100		0.15
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: rs8032859; hg19: chr15-55550755;