12-55975722-A-G

Position:

• chr12-55975722-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002868.4(RAB5B):​c.-93+1583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 149,980 control chromosomes in the GnomAD database, including 4,806 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 (4806 hom., cov: 30)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

Genes affected

RAB5B (HGNC:9784): (RAB5B, member RAS oncogene family) Enables GDP binding activity; GTP-dependent protein binding activity; and GTPase activity. Involved in antigen processing and presentation and plasma membrane to endosome transport. Located in endosome and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB5B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.-93+1583A>G		intron_variant		ENST00000360299.10	NP_002859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB5B	ENST00000360299.10	c.-93+1583A>G		intron_variant		1	NM_002868.4	ENSP00000353444.5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33590 AN: 149928 Hom.: 4808 Cov.: 30

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.224 AC: 33592 AN: 149980 Hom.: 4806 Cov.: 30 AF XY: 0.220 AC XY: 16050 AN XY: 73052

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.251

Alfa AF: 0.295 Hom.: 4904

Bravo AF: 0.214

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs773107; hg19: chr12-56369506;