rs4800947

Positions:

• chr18-54734409-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB27B	NM_001375327.1	c.-20+16268T>C		intron_variant			NP_001362256.1
RAB27B	XM_006722518.2	c.-625+16268T>C		intron_variant			XP_006722581.1
RAB27B	XM_017025913.2	c.-829+16268T>C		intron_variant			XP_016881402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB27B	ENST00000586570.5	c.-20+16268T>C		intron_variant		5		ENSP00000468542

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

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.679

Alfa AF: 0.687 Hom.: 32816

Bravo AF: 0.610

Asia WGS AF: 0.547 AC: 1906 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4800947; hg19: chr18-52401640;