rs1873914

chr12-55985643-G-C

Variant summary

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

The NM_002868.4(RAB5B):c.-92-1226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 453,960 control chromosomes in the GnomAD database, including 27,519 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 0.31 (8291 hom., cov: 32)
  • Exomes 𝑓: 0.35 (19228 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB5B	NM_002868.4	c.-92-1226G>C		intron_variant		ENST00000360299.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB5B	ENST00000360299.10	c.-92-1226G>C		intron_variant		1	NM_002868.4	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47674 AN: 151964 Hom.: 8291 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.348 AC: 104935 AN: 301878 Hom.: 19228 Cov.: 0 AF XY: 0.342 AC XY: 58829 AN XY: 171988

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.314 AC: 47687 AN: 152082 Hom.: 8291 Cov.: 32 AF XY: 0.310 AC XY: 23042 AN XY: 74354

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.320

Alfa AF: 0.353 Hom.: 1235

Bravo AF: 0.305

Asia WGS AF: 0.205 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.8
Dann	Benign	0.88

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: rs1873914; hg19: chr12-56379427;