rs9920165

Variant names:

• chr15-55212141-A-G
• rs9920165
• NM_183235.3:c.468-6436T>C

Variant summary

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

The NM_183235.3(RAB27A):​c.468-6436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,134 control chromosomes in the GnomAD database, including 982 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 0.11 (982 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183235.3. 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_183235.3	MANE Select	c.468-6436T>C		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.468-6436T>C		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.468-6436T>C		intron	N/A	NP_001425901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.468-6436T>C		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.468-6436T>C		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.468-6436T>C		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16928 AN: 152016 Hom.: 981 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16937 AN: 152134 Hom.: 982 Cov.: 31 AF XY: 0.110 AC XY: 8219 AN XY: 74384

African (AFR) AF: 0.120 AC: 4976 AN: 41478

American (AMR) AF: 0.0831 AC: 1270 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.111 AC: 573 AN: 5182

South Asian (SAS) AF: 0.162 AC: 779 AN: 4820

European-Finnish (FIN) AF: 0.0934 AC: 989 AN: 10586

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7695 AN: 67998

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.111 Hom.: 289

Bravo AF: 0.109

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-1.5
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: rs9920165; hg19: chr15-55504339;