rs2311120

Variant names:

• chr18-54809892-A-G
• rs2311120
• NM_001375327.1:c.-19-67675A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAB27B	NM_001375327.1	c.-19-67675A>G		intron_variant	Intron 2 of 6		NP_001362256.1
RAB27B	XM_017025913.2	c.-828-18204A>G		intron_variant	Intron 2 of 8		XP_016881402.1
RAB27B	XM_017025914.2	c.-223-52128A>G		intron_variant	Intron 2 of 7		XP_016881403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27B	ENST00000586570.5	c.-19-67675A>G		intron_variant	Intron 2 of 4	5		ENSP00000468542.1

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

African (AFR) AF: 0.339 AC: 14061 AN: 41492

American (AMR) AF: 0.265 AC: 4057 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3470

East Asian (EAS) AF: 0.0806 AC: 417 AN: 5174

South Asian (SAS) AF: 0.328 AC: 1579 AN: 4818

European-Finnish (FIN) AF: 0.183 AC: 1936 AN: 10570

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15031 AN: 67984

Other (OTH) AF: 0.235 AC: 497 AN: 2116

Alfa AF: 0.246 Hom.: 639

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
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs2311120; hg19: chr18-52477123;