rs11629613

Variant names:

• chr15-55285105-T-C
• rs11629613
• NM_183235.3:c.-143+4611A>G

Variant summary

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

The NM_183235.3(RAB27A):​c.-143+4611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,152 control chromosomes in the GnomAD database, including 5,649 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 0.23 (5649 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-143+4611A>G		intron_variant	Intron 1 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-143+4611A>G		intron_variant	Intron 1 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34838 AN: 152034 Hom.: 5640 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.229 AC: 34884 AN: 152152 Hom.: 5649 Cov.: 32 AF XY: 0.231 AC XY: 17205 AN XY: 74388

African (AFR) AF: 0.415 AC: 17204 AN: 41466

American (AMR) AF: 0.245 AC: 3748 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2830 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1194 AN: 4824

European-Finnish (FIN) AF: 0.124 AC: 1316 AN: 10604

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7552 AN: 68008

Other (OTH) AF: 0.216 AC: 456 AN: 2116

Alfa AF: 0.197 Hom.: 1244

Bravo AF: 0.249

Asia WGS AF: 0.364 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		-0.64
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: rs11629613; hg19: chr15-55577303;