chr15-55203765-T-C

Variant names:

• chr15-55203765-T-C
• rs1061824
• NM_183235.3:c.*1742A>G

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.*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
• Publications: 10 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=-0.91).
• BP6: Variant 15-55203765-T-C is Benign according to our data. Variant chr15-55203765-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.*1742A>G		3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.*1742A>G		3_prime_UTR	Exon 8 of 8	NP_001425899.1
	RAB27A	NM_001438972.1		c.*1742A>G		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.*1742A>G		3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.*1742A>G		3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000697642.1		c.*1742A>G		3_prime_UTR	Exon 6 of 6	ENSP00000513368.1	P51159-1

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

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.495 AC: 20403 AN: 41230

American (AMR) AF: 0.160 AC: 2430 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 535 AN: 3460

East Asian (EAS) AF: 0.118 AC: 611 AN: 5158

South Asian (SAS) AF: 0.223 AC: 1072 AN: 4804

European-Finnish (FIN) AF: 0.160 AC: 1677 AN: 10470

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12857 AN: 67880

Other (OTH) AF: 0.226 AC: 475 AN: 2100

Alfa AF: 0.204 Hom.: 4854

Bravo AF: 0.277

Asia WGS AF: 0.220 AC: 764 AN: 3476

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1061824; hg19: chr15-55495963;