rs705699

chr12-55991020-G-A

Variant summary

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

The NM_002868.4(RAB5B):c.438+216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 584,428 control chromosomes in the GnomAD database, including 43,858 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 0.40 (12359 hom., cov: 32)
  • Exomes 𝑓: 0.37 (31499 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB5B	NM_002868.4	c.438+216G>A		intron_variant		ENST00000360299.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB5B	ENST00000360299.10	c.438+216G>A		intron_variant		1	NM_002868.4	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60585 AN: 151892 Hom.: 12334 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.373 AC: 161300 AN: 432418 Hom.: 31499 Cov.: 6 AF XY: 0.367 AC XY: 82292 AN XY: 224312

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.399 AC: 60666 AN: 152010 Hom.: 12359 Cov.: 32 AF XY: 0.393 AC XY: 29170 AN XY: 74306

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.378

Alfa AF: 0.399 Hom.: 20813

Bravo AF: 0.402

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs705699; hg19: chr12-56384804;