chr12-55990903-T-C

Variant names:

• chr12-55990903-T-C
• rs705698
• NM_002868.4:c.438+99T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002868.4(RAB5B):​c.438+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,427,948 control chromosomes in the GnomAD database, including 68,954 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 (5149 hom., cov: 32)
  • Exomes 𝑓: 0.31 (63805 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 28 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	NM_002868.4	MANE Select	c.438+99T>C		intron	N/A	NP_002859.1	P61020-1
	RAB5B	NM_001414458.1		c.681+99T>C		intron	N/A	NP_001401387.1
	RAB5B	NM_001252036.2		c.438+99T>C		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.438+99T>C		intron	N/A	ENSP00000353444.5	P61020-1
	RAB5B	ENST00000553116.5	TSL:1	c.438+99T>C		intron	N/A	ENSP00000450168.1	P61020-1
	RAB5B	ENST00000549505.5	TSL:1	n.*64+99T>C		intron	N/A	ENSP00000450285.1	F8VPW9

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36481 AN: 151984 Hom.: 5150 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.311 AC: 396570 AN: 1275846 Hom.: 63805 Cov.: 17 AF XY: 0.309 AC XY: 195558 AN XY: 633828

African (AFR) AF: 0.0802 AC: 2320 AN: 28936

American (AMR) AF: 0.211 AC: 7929 AN: 37574

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 6813 AN: 21194

East Asian (EAS) AF: 0.211 AC: 7924 AN: 37558

South Asian (SAS) AF: 0.225 AC: 16804 AN: 74838

European-Finnish (FIN) AF: 0.295 AC: 14319 AN: 48550

Middle Eastern (MID) AF: 0.231 AC: 867 AN: 3760

European-Non Finnish (NFE) AF: 0.334 AC: 323962 AN: 970446

Other (OTH) AF: 0.295 AC: 15632 AN: 52990

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152102 Hom.: 5149 Cov.: 32 AF XY: 0.237 AC XY: 17585 AN XY: 74342

African (AFR) AF: 0.0895 AC: 3718 AN: 41536

American (AMR) AF: 0.229 AC: 3498 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1166 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4818

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10576

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21813 AN: 67960

Other (OTH) AF: 0.259 AC: 545 AN: 2108

Alfa AF: 0.251 Hom.: 1513

Bravo AF: 0.232

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		1.2
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: rs705698; hg19: chr12-56384687; COSMIC: COSV64365326; COSMIC: COSV64365326;