chr12-55991020-G-A

Variant names:

• chr12-55991020-G-A
• rs705699
• NM_002868.4:c.438+216G>A

Variant summary

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

The NM_002868.4(RAB5B):​c.438+216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 584,428 control chromosomes in the GnomAD database, including 43,858 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 0.40 (12359 hom., cov: 32)
  • Exomes 𝑓: 0.37 (31499 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 54 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB5B	NM_002868.4	c.438+216G>A		intron_variant	Intron 4 of 5	ENST00000360299.10	NP_002859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB5B	ENST00000360299.10	c.438+216G>A		intron_variant	Intron 4 of 5	1	NM_002868.4	ENSP00000353444.5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60585 AN: 151892 Hom.: 12334 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.373 AC: 161300 AN: 432418 Hom.: 31499 Cov.: 6 AF XY: 0.367 AC XY: 82292 AN XY: 224312

African (AFR) AF: 0.462 AC: 5687 AN: 12320

American (AMR) AF: 0.301 AC: 4999 AN: 16604

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 4751 AN: 12254

East Asian (EAS) AF: 0.221 AC: 6028 AN: 27334

South Asian (SAS) AF: 0.273 AC: 10977 AN: 40148

European-Finnish (FIN) AF: 0.380 AC: 9254 AN: 24358

Middle Eastern (MID) AF: 0.310 AC: 559 AN: 1804

European-Non Finnish (NFE) AF: 0.402 AC: 110071 AN: 273658

Other (OTH) AF: 0.375 AC: 8974 AN: 23938

GnomAD4 genome AF: 0.399 AC: 60666 AN: 152010 Hom.: 12359 Cov.: 32 AF XY: 0.393 AC XY: 29170 AN XY: 74306

African (AFR) AF: 0.462 AC: 19132 AN: 41442

American (AMR) AF: 0.325 AC: 4969 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1259 AN: 5190

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3820 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27333 AN: 67934

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.400 Hom.: 34686

Bravo AF: 0.402

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs705699; hg19: chr12-56384804;