rs7167572

Positions:

• chr15-55282682-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.-143+7034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,036 control chromosomes in the GnomAD database, including 6,806 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 (6806 hom., cov: 31)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.-143+7034G>A		intron_variant		ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.-143+7034G>A		intron_variant		1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40344 AN: 151918 Hom.: 6808 Cov.: 31

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.265 AC: 40329 AN: 152036 Hom.: 6806 Cov.: 31 AF XY: 0.262 AC XY: 19462 AN XY: 74298

Gnomad4 AFR AF: 0.0862

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.265

Alfa AF: 0.357 Hom.: 5380

Bravo AF: 0.249

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7167572; hg19: chr15-55574880;