rs11171710

Variant names:

• chr12-55974294-G-A
• rs11171710
• NM_002868.4:c.-93+155G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-55974294-G-A
• chr12-55974294-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_Supporting BA1

The NM_001414458.1(RAB5B):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,078 control chromosomes in the GnomAD database, including 11,841 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 0.37 (11841 hom., cov: 32)
• Consequence: RAB5B NM_001414458.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 36 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 -7 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 82 codons. Genomic position: 55986961. Lost 0.274 part of the original CDS.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414458.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	NM_002868.4	MANE Select	c.-93+155G>A		intron	N/A	NP_002859.1	P61020-1
	RAB5B	NM_001414458.1		c.3G>A	p.Met1?	start_lost	Exon 1 of 7	NP_001401387.1
	RAB5B	NM_001252036.2		c.-93+294G>A		intron	N/A	NP_001238965.1	P61020-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	ENST00000360299.10	TSL:1 MANE Select	c.-93+155G>A		intron	N/A	ENSP00000353444.5	P61020-1
	RAB5B	ENST00000553116.5	TSL:1	c.-93+294G>A		intron	N/A	ENSP00000450168.1	P61020-1
	RAB5B	ENST00000549505.5	TSL:1	n.-93+155G>A		intron	N/A	ENSP00000450285.1	F8VPW9

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55563 AN: 151960 Hom.: 11845 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.365 AC: 55554 AN: 152078 Hom.: 11841 Cov.: 32 AF XY: 0.370 AC XY: 27469 AN XY: 74326

African (AFR) AF: 0.132 AC: 5481 AN: 41552

American (AMR) AF: 0.427 AC: 6539 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2826 AN: 5136

South Asian (SAS) AF: 0.380 AC: 1828 AN: 4810

European-Finnish (FIN) AF: 0.463 AC: 4907 AN: 10588

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31080 AN: 67902

Other (OTH) AF: 0.421 AC: 890 AN: 2112

Alfa AF: 0.436 Hom.: 25100

Bravo AF: 0.357

Asia WGS AF: 0.412 AC: 1432 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		2.5
PromoterAI		0.0066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11171710; hg19: chr12-56368078;