12-55996852-A-G

Variant names:

• chr12-55996852-A-G
• rs705702
• NM_002868.4:c.*4640A>G

Variant summary

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

The NM_002868.4(RAB5B):​c.*4640A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,990 control chromosomes in the GnomAD database, including 5,180 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 0.24 (5180 hom., cov: 31)
• Consequence: RAB5B NM_002868.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 74 publications found

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

Our verdict: Benign. The variant received -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 = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.*4640A>G		downstream_gene_variant		ENST00000360299.10	NP_002859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB5B	ENST00000360299.10	c.*4640A>G		downstream_gene_variant		1	NM_002868.4	ENSP00000353444.5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36552 AN: 151872 Hom.: 5181 Cov.: 31

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.240 AC: 36553 AN: 151990 Hom.: 5180 Cov.: 31 AF XY: 0.237 AC XY: 17623 AN XY: 74288

African (AFR) AF: 0.0883 AC: 3659 AN: 41450

American (AMR) AF: 0.237 AC: 3619 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5160

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4808

European-Finnish (FIN) AF: 0.286 AC: 3022 AN: 10564

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21801 AN: 67950

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.279 Hom.: 11400

Bravo AF: 0.234

Asia WGS AF: 0.179 AC: 625 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	2.6
DANN	Benign	0.47
PhyloP100		-2.3
PromoterAI		-0.0058	Neutral

Splicing

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

Other links and lift over

dbSNP: rs705702; hg19: chr12-56390636;