12-55976127-A-G

Variant names:

• chr12-55976127-A-G
• rs773108
• NM_002868.4:c.-93+1988A>G

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+1988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,156 control chromosomes in the GnomAD database, including 5,113 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 (5113 hom., cov: 31)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 23 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 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+1988A>G		intron	N/A	NP_002859.1
	RAB5B	NM_001414458.1		c.48+1788A>G		intron	N/A	NP_001401387.1
	RAB5B	NM_001252036.2		c.-93+2127A>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+1988A>G		intron	N/A	ENSP00000353444.5
	RAB5B	ENST00000553116.5	TSL:1	c.-93+2127A>G		intron	N/A	ENSP00000450168.1
	RAB5B	ENST00000549505.5	TSL:1	n.-93+1988A>G		intron	N/A	ENSP00000450285.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36246 AN: 152038 Hom.: 5114 Cov.: 31

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.238 AC: 36248 AN: 152156 Hom.: 5113 Cov.: 31 AF XY: 0.235 AC XY: 17466 AN XY: 74376

African (AFR) AF: 0.0867 AC: 3603 AN: 41538

American (AMR) AF: 0.228 AC: 3490 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1166 AN: 5180

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4828

European-Finnish (FIN) AF: 0.285 AC: 3015 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21731 AN: 67980

Other (OTH) AF: 0.257 AC: 541 AN: 2104

Alfa AF: 0.255 Hom.: 1519

Bravo AF: 0.231

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		-0.83
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: rs773108; hg19: chr12-56369911;