rs1050931

Variant names:

• chr15-55205493-G-A
• rs1050931
• NM_183235.3:c.*14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_183235.3(RAB27A):​c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,611,066 control chromosomes in the GnomAD database, including 38,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7077 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31137 hom.)
• Consequence: RAB27A NM_183235.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.101
• Publications: 20 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-55205493-G-A is Benign according to our data. Variant chr15-55205493-G-A is described in ClinVar as Benign. ClinVar VariationId is 259442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	NM_183235.3	MANE Select	c.*14C>T		3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.*14C>T		3_prime_UTR	Exon 8 of 8	NP_001425899.1
	RAB27A	NM_001438972.1		c.*14C>T		3_prime_UTR	Exon 7 of 7	NP_001425901.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.*14C>T		3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.*14C>T		3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000564609.5	TSL:1	c.*14C>T		3_prime_UTR	Exon 7 of 7	ENSP00000455012.1	P51159-1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40670 AN: 151952 Hom.: 7059 Cov.: 32

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: 0.222

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.193 AC: 48500 AN: 251464 AF XY: 0.193

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.199 AC: 290126 AN: 1458996 Hom.: 31137 Cov.: 32 AF XY: 0.199 AC XY: 144245 AN XY: 725956

African (AFR) AF: 0.509 AC: 16969 AN: 33342

American (AMR) AF: 0.112 AC: 5018 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3889 AN: 26120

East Asian (EAS) AF: 0.0987 AC: 3917 AN: 39686

South Asian (SAS) AF: 0.226 AC: 19514 AN: 86210

European-Finnish (FIN) AF: 0.173 AC: 9242 AN: 53420

Middle Eastern (MID) AF: 0.219 AC: 1261 AN: 5764

European-Non Finnish (NFE) AF: 0.196 AC: 217584 AN: 1109448

Other (OTH) AF: 0.211 AC: 12732 AN: 60284

GnomAD4 genome AF: 0.268 AC: 40728 AN: 152070 Hom.: 7077 Cov.: 32 AF XY: 0.262 AC XY: 19450 AN XY: 74328

African (AFR) AF: 0.495 AC: 20528 AN: 41454

American (AMR) AF: 0.159 AC: 2438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.118 AC: 612 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1705 AN: 10568

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12873 AN: 67976

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.219 Hom.: 1319

Bravo AF: 0.277

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Griscelli syndrome type 2 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.4
DANN	Benign	0.80
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1050931; hg19: chr15-55497691; COSMIC: COSV61015156; COSMIC: COSV61015156;