15-55203581-A-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.*1926T>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 0.308 in 128,488 control chromosomes in the GnomAD database, including 6,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (6930 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: 0.0140

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=-1.02).
• BP6: Variant 15-55203581-A-T is Benign according to our data. Variant chr15-55203581-A-T is described in ClinVar as [Benign]. Clinvar id is 316613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.*1926T>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.*1926T>A		3_prime_UTR_variant	7/7	1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 39533 AN: 128444 Hom.: 6914 Cov.: 24

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.271

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.308 AC: 39581 AN: 128488 Hom.: 6930 Cov.: 24 AF XY: 0.306 AC XY: 18854 AN XY: 61658

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.269

Alfa AF: 0.000306 Hom.: 1

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	-1.0
Cadd	Benign	0.77
Dann	Benign	0.071

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: rs8028801; hg19: chr15-55495779;