chr15-55312954-T-C

Variant names:

• chr15-55312954-T-C
• rs11636687
• NM_001438970.1:c.-232+5977A>G

Variant summary

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

The NM_001438970.1(RAB27A):​c.-232+5977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,996 control chromosomes in the GnomAD database, including 6,789 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 0.27 (6789 hom., cov: 32)
• Consequence: RAB27A NM_001438970.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438970.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	NM_001438970.1		c.-232+5977A>G		intron	N/A	NP_001425899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000563262.5	TSL:3	c.-112+1085A>G		intron	N/A	ENSP00000457595.1
	RAB27A	ENST00000561545.1	TSL:3	n.321+1066A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41651 AN: 151878 Hom.: 6782 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.274 AC: 41686 AN: 151996 Hom.: 6789 Cov.: 32 AF XY: 0.275 AC XY: 20426 AN XY: 74312

African (AFR) AF: 0.426 AC: 17622 AN: 41400

American (AMR) AF: 0.282 AC: 4298 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2827 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1853 AN: 10586

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12149 AN: 67988

Other (OTH) AF: 0.264 AC: 556 AN: 2106

Alfa AF: 0.210 Hom.: 15985

Bravo AF: 0.291

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.79
PhyloP100		-0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11636687; hg19: chr15-55605152;