rs17528736

chr12-55974734-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002868.4(RAB5B):c.-93+595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 152,202 control chromosomes in the GnomAD database, including 65 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 0.024 (65 hom., cov: 32)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0236 (3592/152202) while in subpopulation NFE AF= 0.0355 (2413/68012). AF 95% confidence interval is 0.0343. There are 65 homozygotes in gnomad4. There are 1775 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB5B	NM_002868.4	c.-93+595C>T		intron_variant		ENST00000360299.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB5B	ENST00000360299.10	c.-93+595C>T		intron_variant		1	NM_002868.4	P1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3594 AN: 152084 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00628

Gnomad AMI AF: 0.0673

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0181

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

GnomAD4 genome AF: 0.0236 AC: 3592 AN: 152202 Hom.: 65 Cov.: 32 AF XY: 0.0239 AC XY: 1775 AN XY: 74406

Gnomad4 AFR AF: 0.00624

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0315 Hom.: 119

Bravo AF: 0.0212

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
Dann	Benign	0.27

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: rs17528736; hg19: chr12-56368518;