rs773107

Variant names:

• chr12-55975722-A-G
• rs773107
• NM_002868.4:c.-93+1583A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-55975722-A-G
• chr12-55975722-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002868.4(RAB5B):​c.-93+1583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 149,980 control chromosomes in the GnomAD database, including 4,806 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 0.22 (4806 hom., cov: 30)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 38 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

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+1583A>G		intron	N/A	NP_002859.1
	RAB5B	NM_001414458.1		c.48+1383A>G		intron	N/A	NP_001401387.1
	RAB5B	NM_001252036.2		c.-93+1722A>G		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+1583A>G		intron	N/A	ENSP00000353444.5
	RAB5B	ENST00000553116.5	TSL:1	c.-93+1722A>G		intron	N/A	ENSP00000450168.1
	RAB5B	ENST00000549505.5	TSL:1	n.-93+1583A>G		intron	N/A	ENSP00000450285.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33590 AN: 149928 Hom.: 4808 Cov.: 30

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.224 AC: 33592 AN: 149980 Hom.: 4806 Cov.: 30 AF XY: 0.220 AC XY: 16050 AN XY: 73052

African (AFR) AF: 0.0583 AC: 2363 AN: 40566

American (AMR) AF: 0.227 AC: 3422 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1128 AN: 3462

East Asian (EAS) AF: 0.0716 AC: 366 AN: 5112

South Asian (SAS) AF: 0.191 AC: 910 AN: 4756

European-Finnish (FIN) AF: 0.276 AC: 2765 AN: 10034

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.319 AC: 21588 AN: 67712

Other (OTH) AF: 0.251 AC: 520 AN: 2072

Alfa AF: 0.289 Hom.: 7776

Bravo AF: 0.214

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.69
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs773107; hg19: chr12-56369506;