rs4800947

Variant names:

• chr18-54734409-T-C
• rs4800947
• NM_001375327.1:c.-20+16268T>C

Variant summary

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

The NM_001375327.1(RAB27B):​c.-20+16268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,008 control chromosomes in the GnomAD database, including 31,011 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 0.63 (31011 hom., cov: 31)
• Consequence: RAB27B NM_001375327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375327.1. 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
	RAB27B	NM_001375327.1		c.-20+16268T>C		intron	N/A	NP_001362256.1	O00194

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB27B	ENST00000895850.1		c.-20+16270T>C		intron	N/A	ENSP00000565909.1
	RAB27B	ENST00000962461.1		c.-20+16264T>C		intron	N/A	ENSP00000632520.1
	RAB27B	ENST00000586570.5	TSL:5	c.-20+16268T>C		intron	N/A	ENSP00000468542.1	K7ES41

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95346 AN: 151890 Hom.: 31020 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.627 AC: 95351 AN: 152008 Hom.: 31011 Cov.: 31 AF XY: 0.623 AC XY: 46281 AN XY: 74272

African (AFR) AF: 0.459 AC: 19041 AN: 41450

American (AMR) AF: 0.593 AC: 9045 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2752 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2981 AN: 5162

South Asian (SAS) AF: 0.542 AC: 2608 AN: 4808

European-Finnish (FIN) AF: 0.704 AC: 7439 AN: 10572

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49370 AN: 67986

Other (OTH) AF: 0.679 AC: 1433 AN: 2112

Alfa AF: 0.692 Hom.: 45460

Bravo AF: 0.610

Asia WGS AF: 0.547 AC: 1906 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.091
DANN	Benign	0.72
PhyloP100		-2.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4800947;

hg19: chr18-52401640;