rs28620827

Variant names:

• chr15-55203603-T-A
• rs28620827
• NM_183235.3:c.*1904A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-55203603-T-A
• chr15-55203603-T-C
• chr15-55203603-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.*1904A>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 0.131 in 146,292 control chromosomes in the GnomAD database, including 1,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1342 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAB27A NM_183235.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.301
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 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.*1904A>T		3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.*1904A>T		3_prime_UTR	Exon 8 of 8	NP_001425899.1
	RAB27A	NM_001438972.1		c.*1904A>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.*1904A>T		3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.*1904A>T		3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000899597.1		c.*1904A>T		3_prime_UTR	Exon 7 of 7	ENSP00000569656.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19097 AN: 146200 Hom.: 1337 Cov.: 24

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.124

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 178 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 140

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 20

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: 148

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.131 AC: 19118 AN: 146292 Hom.: 1342 Cov.: 24 AF XY: 0.130 AC XY: 9251 AN XY: 71184

African (AFR) AF: 0.132 AC: 5164 AN: 39182

American (AMR) AF: 0.0992 AC: 1461 AN: 14732

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 391 AN: 3428

East Asian (EAS) AF: 0.117 AC: 591 AN: 5050

South Asian (SAS) AF: 0.184 AC: 849 AN: 4614

European-Finnish (FIN) AF: 0.118 AC: 1089 AN: 9258

Middle Eastern (MID) AF: 0.115 AC: 33 AN: 288

European-Non Finnish (NFE) AF: 0.136 AC: 9054 AN: 66816

Other (OTH) AF: 0.123 AC: 250 AN: 2028

Alfa AF: 0.0460 Hom.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.93
CADD	Benign	2.0
DANN	Benign	0.29
PhyloP100		-0.30
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: rs28620827; hg19: chr15-55495801;