15-55203581-A-T

Variant names:

• chr15-55203581-A-T
• rs8028801
• NM_183235.3:c.*1926T>A

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 0 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=-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 VariationId is 316613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 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.*1926T>A		3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.*1926T>A		3_prime_UTR	Exon 8 of 8	NP_001425899.1
	RAB27A	NM_001438972.1		c.*1926T>A		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.*1926T>A		3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.*1926T>A		3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000899597.1		c.*1926T>A		3_prime_UTR	Exon 7 of 7	ENSP00000569656.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.530 AC: 19815 AN: 37384

American (AMR) AF: 0.193 AC: 2366 AN: 12246

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 539 AN: 2954

East Asian (EAS) AF: 0.144 AC: 607 AN: 4224

South Asian (SAS) AF: 0.263 AC: 1053 AN: 4008

European-Finnish (FIN) AF: 0.221 AC: 1496 AN: 6764

Middle Eastern (MID) AF: 0.215 AC: 53 AN: 246

European-Non Finnish (NFE) AF: 0.220 AC: 12767 AN: 58108

Other (OTH) AF: 0.269 AC: 460 AN: 1710

Alfa AF: 0.000306 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Griscelli syndrome type 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.071
PhyloP100		0.014
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: rs8028801; hg19: chr15-55495779;