rs9972478

chr15-55267534-A-Cchr15-55267534-A-Gchr15-55267534-A-T

Variant summary

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

The NM_183235.3(RAB27A):c.-23+2631T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,046 control chromosomes in the GnomAD database, including 25,271 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 0.56 (25271 hom., cov: 32)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27A	NM_183235.3	c.-23+2631T>G		intron_variant		ENST00000336787.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+2631T>G		intron_variant		1	NM_183235.3	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85266 AN: 151928 Hom.: 25214 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.562 AC: 85384 AN: 152046 Hom.: 25271 Cov.: 32 AF XY: 0.557 AC XY: 41427 AN XY: 74320

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.537

Alfa AF: 0.318 Hom.: 665

Bravo AF: 0.588

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.9
Dann	Benign	0.45

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: rs9972478; hg19: chr15-55559732;