rs7165491

Variant names:

• chr15-55208257-A-C
• rs7165491
• NM_183235.3:c.468-2552T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-55208257-A-C
• chr15-55208257-A-T

Variant summary

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

The NM_183235.3(RAB27A):​c.468-2552T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,118 control chromosomes in the GnomAD database, including 10,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (10659 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 8 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.468-2552T>G		intron_variant	Intron 6 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.468-2552T>G		intron_variant	Intron 6 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47094 AN: 152000 Hom.: 10627 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47184 AN: 152118 Hom.: 10659 Cov.: 32 AF XY: 0.303 AC XY: 22534 AN XY: 74382

African (AFR) AF: 0.643 AC: 26612 AN: 41414

American (AMR) AF: 0.174 AC: 2661 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.118 AC: 614 AN: 5190

South Asian (SAS) AF: 0.223 AC: 1078 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1703 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12928 AN: 68002

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.152 Hom.: 500

Bravo AF: 0.326

Asia WGS AF: 0.229 AC: 796 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.20
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)		0.0		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: rs7165491; hg19: chr15-55500455;