rs4774760

Variant names:

• chr15-55297014-T-A
• rs4774760
• NM_001438970.1:c.-232+21917A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-55297014-T-A
• chr15-55297014-T-C
• chr15-55297014-T-G

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+21917A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,982 control chromosomes in the GnomAD database, including 6,847 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 0.27 (6847 hom., cov: 32)
• Consequence: RAB27A NM_001438970.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 11 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_001438970.1	c.-232+21917A>T		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+17025A>T		intron_variant	Intron 2 of 5	3		ENSP00000457595.1
RAB27A	ENST00000561545.1	n.322-6618A>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41410 AN: 151864 Hom.: 6835 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.273 AC: 41456 AN: 151982 Hom.: 6847 Cov.: 32 AF XY: 0.271 AC XY: 20162 AN XY: 74312

African (AFR) AF: 0.433 AC: 17921 AN: 41418

American (AMR) AF: 0.283 AC: 4315 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2839 AN: 5174

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4826

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10560

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12068 AN: 67960

Other (OTH) AF: 0.266 AC: 562 AN: 2114

Alfa AF: 0.213 Hom.: 482

Bravo AF: 0.293

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs4774760; hg19: chr15-55589212;