rs12901464

Variant names:

• chr15-55299714-A-G
• rs12901464
• NM_001438970.1:c.-232+19217T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-55299714-A-G
• chr15-55299714-A-T

Variant summary

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

The NM_001438970.1(RAB27A):​c.-232+19217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,288 control chromosomes in the GnomAD database, including 226 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 0.043 (226 hom., cov: 31)
• Consequence: RAB27A NM_001438970.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 2 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_001438970.1	c.-232+19217T>C		intron_variant	Intron 1 of 7		NP_001425899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000563262.5	c.-112+14325T>C		intron_variant	Intron 2 of 5	3		ENSP00000457595.1
RAB27A	ENST00000561545.1	n.322-9318T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6592 AN: 152170 Hom.: 226 Cov.: 31

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00922

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0427

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

GnomAD4 genome AF: 0.0433 AC: 6594 AN: 152288 Hom.: 226 Cov.: 31 AF XY: 0.0456 AC XY: 3395 AN XY: 74472

African (AFR) AF: 0.00839 AC: 349 AN: 41580

American (AMR) AF: 0.0529 AC: 810 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3472

East Asian (EAS) AF: 0.00924 AC: 48 AN: 5196

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4828

European-Finnish (FIN) AF: 0.0978 AC: 1035 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3655 AN: 68010

Other (OTH) AF: 0.0423 AC: 89 AN: 2106

Alfa AF: 0.0481 Hom.: 27

Bravo AF: 0.0374

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.8
DANN	Benign	0.95
PhyloP100		0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12901464; hg19: chr15-55591912;