chr15-55203765-T-C

Position:

• chr15-55203765-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_183235.3(RAB27A):​c.*1742A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,548 control chromosomes in the GnomAD database, including 7,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7042 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: RAB27A NM_183235.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.65

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-55203765-T-C is Benign according to our data. Variant chr15-55203765-T-C is described in ClinVar as [Benign]. Clinvar id is 316618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.*1742A>G		3_prime_UTR_variant	7/7	ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.*1742A>G		3_prime_UTR_variant	7/7	1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40486 AN: 151422 Hom.: 7024 Cov.: 30

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.268 AC: 40544 AN: 151540 Hom.: 7042 Cov.: 30 AF XY: 0.261 AC XY: 19340 AN XY: 74038

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.226

Alfa AF: 0.192 Hom.: 3189

Bravo AF: 0.277

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Griscelli syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1061824; hg19: chr15-55495963;