rs2006776

Variant names:

• chr18-54837267-A-G
• rs2006776
• NM_004163.4:c.-20+8567A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004163.4(RAB27B):​c.-20+8567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,034 control chromosomes in the GnomAD database, including 4,007 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 0.22 (4007 hom., cov: 31)
• Consequence: RAB27B NM_004163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004163.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27B	NM_004163.4	MANE Select	c.-20+8567A>G		intron	N/A	NP_004154.2
	RAB27B	NM_001375327.1		c.-19-40300A>G		intron	N/A	NP_001362256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27B	ENST00000262094.10	TSL:1 MANE Select	c.-20+8567A>G		intron	N/A	ENSP00000262094.4
	RAB27B	ENST00000895850.1		c.-19-40300A>G		intron	N/A	ENSP00000565909.1
	RAB27B	ENST00000962461.1		c.-19-40300A>G		intron	N/A	ENSP00000632520.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33090 AN: 151918 Hom.: 4009 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.218 AC: 33097 AN: 152034 Hom.: 4007 Cov.: 31 AF XY: 0.216 AC XY: 16024 AN XY: 74348

African (AFR) AF: 0.316 AC: 13112 AN: 41446

American (AMR) AF: 0.187 AC: 2850 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3470

East Asian (EAS) AF: 0.0768 AC: 398 AN: 5184

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10588

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12547 AN: 67948

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.197 Hom.: 9911

Bravo AF: 0.222

Asia WGS AF: 0.192 AC: 667 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.77
PhyloP100		-0.029
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: rs2006776; hg19: chr18-52504498;