chr15-55225033-C-G

Variant names:

• chr15-55225033-C-G
• rs7181237
• NM_183235.3:c.344-1021G>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.344-1021G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,054 control chromosomes in the GnomAD database, including 14,119 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 0.37 (14119 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.344-1021G>C		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.344-1021G>C		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.344-1021G>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.344-1021G>C		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.344-1021G>C		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.344-1021G>C		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56914 AN: 151936 Hom.: 14083 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.375 AC: 57014 AN: 152054 Hom.: 14119 Cov.: 32 AF XY: 0.371 AC XY: 27578 AN XY: 74322

African (AFR) AF: 0.708 AC: 29334 AN: 41440

American (AMR) AF: 0.335 AC: 5125 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3472

East Asian (EAS) AF: 0.122 AC: 633 AN: 5178

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10558

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16116 AN: 67972

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.314 Hom.: 1241

Bravo AF: 0.397

Asia WGS AF: 0.248 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.44
PhyloP100		-0.21
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: rs7181237; hg19: chr15-55517231;