Genetic Variant NM_002868.4:c.-92-1226G>C (chr12-55985643-G-C) – 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.-92-1226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 453,960 control chromosomes in the GnomAD database, including 27,519 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 0.31 ( 8291 hom., cov: 32)

Exomes 𝑓: 0.35 ( 19228 hom. )

Consequence

RAB5B
NM_002868.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Publications

46 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:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB5B	NM_002868.4 link	c.-92-1226G>C		intron_variant	Intron 1 of 5	ENST00000360299.10	NP_002859.1	P61020-1A0A024RB09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB5B	ENST00000360299.10 link	c.-92-1226G>C		intron_variant	Intron 1 of 5	1	NM_002868.4	ENSP00000353444.5		P61020-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47674

AN:

151964

Hom.:

8291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.348

AC:

104935

AN:

301878

Hom.:

19228

Cov.:

AF XY:

0.342

AC XY:

58829

AN XY:

171988

show subpopulations

African (AFR)

AF:

0.171

AC:

1459

AN:

8556

American (AMR)

AF:

0.267

AC:

7225

AN:

27020

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

4009

AN:

10744

East Asian (EAS)

AF:

0.226

AC:

2062

AN:

9128

South Asian (SAS)

AF:

0.276

AC:

16368

AN:

59378

European-Finnish (FIN)

AF:

0.379

AC:

4662

AN:

12314

Middle Eastern (MID)

AF:

0.240

AC:

664

AN:

2764

European-Non Finnish (NFE)

AF:

0.402

AC:

63495

AN:

157854

Other (OTH)

AF:

0.353

AC:

4991

AN:

14120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3096

6192

9289

12385

15481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.314

AC:

47687

AN:

152082

Hom.:

8291

Cov.:

AF XY:

0.310

AC XY:

23042

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.169

AC:

7005

AN:

41484

American (AMR)

AF:

0.290

AC:

4425

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1359

AN:

3470

East Asian (EAS)

AF:

0.230

AC:

1194

AN:

5182

South Asian (SAS)

AF:

0.269

AC:

1297

AN:

4816

European-Finnish (FIN)

AF:

0.363

AC:

3836

AN:

10574

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.401

AC:

27257

AN:

67966

Other (OTH)

AF:

0.320

AC:

676

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.353

Hom.:

1235

Bravo

AF:

0.305

Asia WGS

AF:

0.205

AC:

716

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.8

(source)

DANN

Benign

0.88

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over