rs9972478

Variant names:

• chr15-55267534-A-C
• rs9972478
• NM_183235.3:c.-23+2631T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-55267534-A-C
• chr15-55267534-A-G
• chr15-55267534-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.-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
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	NM_183235.3	MANE Select	c.-23+2631T>G		intron	N/A	NP_899058.1	P51159-1
	RAB27A	NM_001438970.1		c.-112+2631T>G		intron	N/A	NP_001425899.1
	RAB27A	NM_001438972.1		c.-23+2631T>G		intron	N/A	NP_001425901.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27A	ENST00000336787.6	TSL:1 MANE Select	c.-23+2631T>G		intron	N/A	ENSP00000337761.1	P51159-1
	RAB27A	ENST00000396307.6	TSL:1	c.-23+2631T>G		intron	N/A	ENSP00000379601.2	P51159-1
	RAB27A	ENST00000564609.5	TSL:1	c.-112+2631T>G		intron	N/A	ENSP00000455012.1	P51159-1

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

African (AFR) AF: 0.729 AC: 30228 AN: 41464

American (AMR) AF: 0.612 AC: 9350 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3851 AN: 5166

South Asian (SAS) AF: 0.480 AC: 2315 AN: 4826

European-Finnish (FIN) AF: 0.401 AC: 4237 AN: 10564

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31765 AN: 67950

Other (OTH) AF: 0.537 AC: 1134 AN: 2112

Alfa AF: 0.348 Hom.: 875

Bravo AF: 0.588

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.45
PhyloP100		-0.55
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: rs9972478; hg19: chr15-55559732;