rs8092503

Positions:

• chr18-54812256-A-G

Variant summary

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

The NM_001375327.1(RAB27B):​c.-19-65311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,970 control chromosomes in the GnomAD database, including 4,220 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 0.23 (4220 hom., cov: 32)
• Consequence: RAB27B NM_001375327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

Genes affected

RAB27B (HGNC:9767): (RAB27B, member RAS oncogene family) Enables guanyl ribonucleotide binding activity; myosin V binding activity; and protein domain specific binding activity. Involved in multivesicular body sorting pathway and positive regulation of exocytosis. Located in Golgi stack and cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27B	NM_001375327.1	c.-19-65311A>G		intron_variant			NP_001362256.1
RAB27B	XM_006722518.2	c.-624-15840A>G		intron_variant			XP_006722581.1
RAB27B	XM_017025913.2	c.-828-15840A>G		intron_variant			XP_016881402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27B	ENST00000586570.5	c.-19-65311A>G		intron_variant		5		ENSP00000468542

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34607 AN: 151852 Hom.: 4212 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.228 AC: 34651 AN: 151970 Hom.: 4220 Cov.: 32 AF XY: 0.234 AC XY: 17412 AN XY: 74252

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.201

Alfa AF: 0.229 Hom.: 1820

Bravo AF: 0.224

Asia WGS AF: 0.272 AC: 944 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8092503; hg19: chr18-52479487;