15-55203158-T-C

Variant names:

• chr15-55203158-T-C
• rs76970799
• NM_183235.3:c.*2349A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_183235.3(RAB27A):​c.*2349A>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 0.0112 in 152,332 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (37 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RAB27A NM_183235.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-55203158-T-C is Benign according to our data. Variant chr15-55203158-T-C is described in ClinVar as Benign. ClinVar VariationId is 316607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1704/152332) while in subpopulation AFR AF = 0.0391 (1624/41568). AF 95% confidence interval is 0.0375. There are 37 homozygotes in GnomAd4. There are 809 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

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.*2349A>G		3_prime_UTR	Exon 7 of 7	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.*2349A>G		3_prime_UTR	Exon 8 of 8	NP_001425899.1
	RAB27A	NM_001438972.1		c.*2349A>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.*2349A>G		3_prime_UTR	Exon 7 of 7	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.*2349A>G		3_prime_UTR	Exon 6 of 6	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000899597.1		c.*2349A>G		3_prime_UTR	Exon 7 of 7	ENSP00000569656.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1702 AN: 152214 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00669

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0112 AC: 1704 AN: 152332 Hom.: 37 Cov.: 32 AF XY: 0.0109 AC XY: 809 AN XY: 74488

African (AFR) AF: 0.0391 AC: 1624 AN: 41568

American (AMR) AF: 0.00366 AC: 56 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68030

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00162 Hom.: 1

Bravo AF: 0.0125

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Griscelli syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.79
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs76970799; hg19: chr15-55495356;