chr12-55976127-A-G

Position:

• chr12-55976127-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+1988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,156 control chromosomes in the GnomAD database, including 5,113 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 (5113 hom., cov: 31)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.-93+1988A>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+1988A>G		intron_variant		1	NM_002868.4	ENSP00000353444.5

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36246 AN: 152038 Hom.: 5114 Cov.: 31

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.238 AC: 36248 AN: 152156 Hom.: 5113 Cov.: 31 AF XY: 0.235 AC XY: 17466 AN XY: 74376

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.257

Alfa AF: 0.260 Hom.: 1393

Bravo AF: 0.231

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.72

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: rs773108; hg19: chr12-56369911;