NM_183235.3:c.-23+1938T>C

Variant names:

• chr15-55268227-A-G
• rs11071175
• NM_183235.3:c.-23+1938T>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.-23+1938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,722 control chromosomes in the GnomAD database, including 25,515 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 0.56 (25515 hom., cov: 29)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 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.-23+1938T>C		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.-112+1938T>C		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-23+1938T>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.-23+1938T>C		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000396307.6	TSL:1	c.-23+1938T>C		intron	N/A	ENSP00000379601.2
	RAB27A	ENST00000564609.5	TSL:1	c.-112+1938T>C		intron	N/A	ENSP00000455012.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85484 AN: 151604 Hom.: 25458 Cov.: 29

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.564 AC: 85600 AN: 151722 Hom.: 25515 Cov.: 29 AF XY: 0.560 AC XY: 41493 AN XY: 74132

African (AFR) AF: 0.739 AC: 30532 AN: 41324

American (AMR) AF: 0.614 AC: 9358 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1913 AN: 3462

East Asian (EAS) AF: 0.746 AC: 3850 AN: 5162

South Asian (SAS) AF: 0.478 AC: 2301 AN: 4810

European-Finnish (FIN) AF: 0.400 AC: 4199 AN: 10496

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31730 AN: 67916

Other (OTH) AF: 0.539 AC: 1136 AN: 2108

Alfa AF: 0.503 Hom.: 33914

Bravo AF: 0.591

Asia WGS AF: 0.618 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.71
PhyloP100		-1.1
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: rs11071175; hg19: chr15-55560425;