dbSNP rs705699: RAB5B:c.438+216G>A (chr12-55991020-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

54 publications found

Variant links:

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]

RAB5B links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RAB5B	NM_002868.4	MANE Select	c.438+216G>A	intron	N/A	NP_002859.1
RAB5B	NM_001414458.1		c.681+216G>A	intron	N/A	NP_001401387.1
RAB5B	NM_001252036.2		c.438+216G>A	intron	N/A	NP_001238965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RAB5B	ENST00000360299.10	TSL:1 MANE Select	c.438+216G>A	intron	N/A	ENSP00000353444.5
RAB5B	ENST00000553116.5	TSL:1	c.438+216G>A	intron	N/A	ENSP00000450168.1
RAB5B	ENST00000549505.5	TSL:1	n.*64+216G>A	intron	N/A	ENSP00000450285.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60585

AN:

151892

Hom.:

12334

Cov.:

show subpopulations

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.:

AF XY:

0.367

AC XY:

82292

AN XY:

224312

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4658

9317

13975

18634

23292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1248

2496

3744

4992

6240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60666

AN:

152010

Hom.:

12359

Cov.:

AF XY:

0.393

AC XY:

29170

AN XY:

74306

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27333

AN:

67934

Other (OTH)

AF:

0.378

AC:

799

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1880

3760

5641

7521

9401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over