chr15-55282682-C-T

Variant names:

• chr15-55282682-C-T
• rs7167572
• NM_183235.3:c.-143+7034G>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.-143+7034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,036 control chromosomes in the GnomAD database, including 6,806 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 (6806 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.381 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.-143+7034G>A		intron	N/A	NP_899058.1
	RAB27A	NM_001438970.1		c.-231-12398G>A		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-143+6770G>A		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.-143+7034G>A		intron	N/A	ENSP00000337761.1
	RAB27A	ENST00000697642.1		c.-23+7034G>A		intron	N/A	ENSP00000513368.1
	RAB27A	ENST00000697643.1		c.-232+7034G>A		intron	N/A	ENSP00000513369.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40344 AN: 151918 Hom.: 6808 Cov.: 31

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.265 AC: 40329 AN: 152036 Hom.: 6806 Cov.: 31 AF XY: 0.262 AC XY: 19462 AN XY: 74298

African (AFR) AF: 0.0862 AC: 3575 AN: 41482

American (AMR) AF: 0.231 AC: 3525 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3472

East Asian (EAS) AF: 0.0579 AC: 299 AN: 5166

South Asian (SAS) AF: 0.256 AC: 1233 AN: 4810

European-Finnish (FIN) AF: 0.340 AC: 3579 AN: 10540

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26182 AN: 67966

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.355 Hom.: 7275

Bravo AF: 0.249

Asia WGS AF: 0.135 AC: 469 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	0.29
DANN	Benign	0.64
PhyloP100		-2.3
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: rs7167572; hg19: chr15-55574880;