rs17528736

Variant names:

• chr12-55974734-C-T
• rs17528736
• NM_002868.4:c.-93+595C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.85).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	NM_002868.4	MANE Select	c.-93+595C>T		intron	N/A	NP_002859.1
	RAB5B	NM_001414458.1		c.48+395C>T		intron	N/A	NP_001401387.1
	RAB5B	NM_001252036.2		c.-93+734C>T		intron	N/A	NP_001238965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	ENST00000360299.10	TSL:1 MANE Select	c.-93+595C>T		intron	N/A	ENSP00000353444.5
	RAB5B	ENST00000553116.5	TSL:1	c.-93+734C>T		intron	N/A	ENSP00000450168.1
	RAB5B	ENST00000549505.5	TSL:1	n.-93+595C>T		intron	N/A	ENSP00000450285.1

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

African (AFR) AF: 0.00624 AC: 259 AN: 41520

American (AMR) AF: 0.0168 AC: 257 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0242 AC: 117 AN: 4826

European-Finnish (FIN) AF: 0.0338 AC: 358 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2413 AN: 68012

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.0317 Hom.: 246

Bravo AF: 0.0212

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.27
PhyloP100		0.034
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17528736; hg19: chr12-56368518;