rs11171710

Positions:

• chr12-55974294-G-A
• chr12-55974294-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The NM_001414458.1(RAB5B):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,078 control chromosomes in the GnomAD database, including 11,841 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 0.37 (11841 hom., cov: 32)
• Consequence: RAB5B NM_001414458.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.-93+155G>A		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+155G>A		intron_variant		1	NM_002868.4	ENSP00000353444.5

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55563 AN: 151960 Hom.: 11845 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.365 AC: 55554 AN: 152078 Hom.: 11841 Cov.: 32 AF XY: 0.370 AC XY: 27469 AN XY: 74326

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.421

Alfa AF: 0.446 Hom.: 20384

Bravo AF: 0.357

Asia WGS AF: 0.412 AC: 1432 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11171710; hg19: chr12-56368078;