rs2311120

Positions:

• chr18-54809892-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.-19-67675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,112 control chromosomes in the GnomAD database, including 5,344 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 0.25 (5344 hom., cov: 32)
• Consequence: RAB27B NM_001375327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB27B	NM_001375327.1	c.-19-67675A>G		intron_variant
RAB27B	XM_006722518.2	c.-624-18204A>G		intron_variant
RAB27B	XM_017025913.2	c.-828-18204A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB27B	ENST00000586570.5	c.-19-67675A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38630 AN: 151996 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.254 AC: 38642 AN: 152112 Hom.: 5344 Cov.: 32 AF XY: 0.252 AC XY: 18730 AN XY: 74362

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.0806

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.235

Alfa AF: 0.241 Hom.: 584

Bravo AF: 0.262

Asia WGS AF: 0.241 AC: 835 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2311120; hg19: chr18-52477123;