12-55990903-T-C

Position:

• chr12-55990903-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002868.4(RAB5B):​c.438+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,427,948 control chromosomes in the GnomAD database, including 68,954 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 (5149 hom., cov: 32)
  • Exomes 𝑓: 0.31 (63805 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• 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/exons	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.438+99T>C		intron_variant		ENST00000360299.10	NP_002859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB5B	ENST00000360299.10	c.438+99T>C		intron_variant		1	NM_002868.4	ENSP00000353444	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36481 AN: 151984 Hom.: 5150 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.311 AC: 396570 AN: 1275846 Hom.: 63805 Cov.: 17 AF XY: 0.309 AC XY: 195558 AN XY: 633828

Gnomad4 AFR exome AF: 0.0802

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152102 Hom.: 5149 Cov.: 32 AF XY: 0.237 AC XY: 17585 AN XY: 74342

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.259

Alfa AF: 0.255 Hom.: 1387

Bravo AF: 0.232

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.84

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: rs705698; hg19: chr12-56384687; COSMIC: COSV64365326; COSMIC: COSV64365326;