chr15-55242144-C-T

Variant names:

• chr15-55242144-C-T
• rs2444043
• NM_183235.3:c.-22-7188G>A

Variant summary

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

The NM_183235.3(RAB27A):​c.-22-7188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,846 control chromosomes in the GnomAD database, including 21,163 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 0.52 (21163 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-22-7188G>A		intron_variant	Intron 2 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-22-7188G>A		intron_variant	Intron 2 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78921 AN: 151728 Hom.: 21125 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.520 AC: 79014 AN: 151846 Hom.: 21163 Cov.: 31 AF XY: 0.519 AC XY: 38535 AN XY: 74188

African (AFR) AF: 0.562 AC: 23258 AN: 41416

American (AMR) AF: 0.626 AC: 9538 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3468

East Asian (EAS) AF: 0.763 AC: 3940 AN: 5162

South Asian (SAS) AF: 0.527 AC: 2539 AN: 4820

European-Finnish (FIN) AF: 0.439 AC: 4612 AN: 10504

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31357 AN: 67922

Other (OTH) AF: 0.528 AC: 1113 AN: 2106

Alfa AF: 0.495 Hom.: 15732

Bravo AF: 0.538

Asia WGS AF: 0.603 AC: 2097 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.33
PhyloP100		0.98
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: rs2444043; hg19: chr15-55534342;