15-55203500-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_183235.3(RAB27A):c.*2007G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 148,284 control chromosomes in the GnomAD database, including 6,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6849 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAB27A NM_183235.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.776

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-55203500-C-T is Benign according to our data. Variant chr15-55203500-C-T is described in ClinVar as [Benign]. Clinvar id is 316611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.*2007G>A		3_prime_UTR_variant	7/7	ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.*2007G>A		3_prime_UTR_variant	7/7	1	NM_183235.3	P1
RAB27A	ENST00000396307.6	c.*2007G>A		3_prime_UTR_variant	6/6	1		P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 39258 AN: 148188 Hom.: 6831 Cov.: 24

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.225

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 39310 AN: 148284 Hom.: 6849 Cov.: 24 AF XY: 0.259 AC XY: 18669 AN XY: 72212

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.223

Alfa AF: 0.228 Hom.: 609

Bravo AF: 0.277

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Griscelli syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.0
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs6493769; hg19: chr15-55495698; COSMIC: COSV61018251; COSMIC: COSV61018251;