dbSNP rs2275073: RAB25:c.-372C>A (chr1-156061029-C-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_020387.4(RAB25):c.-372C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 173,600 control chromosomes in the GnomAD database, including 37,947 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 0.60 ( 32068 hom., cov: 31)

Exomes 𝑓: 0.71 ( 5879 hom. )

Consequence

RAB25
NM_020387.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373

Publications

7 publications found

Variant links:

Genes affected

RAB25 (HGNC:18238): (RAB25, member RAS oncogene family) The protein encoded by this gene is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Nov 2015]

RAB25 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020387.4. 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
	RAB25	NM_020387.4	MANE Select	c.-372C>A		upstream_gene	N/A	NP_065120.2	P57735
	RAB25	NR_133653.2		n.-131C>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB25	ENST00000361084.10	TSL:1 MANE Select	c.-372C>A	upstream_gene	N/A	ENSP00000354376.5	P57735
RAB25	ENST00000876131.1		c.-372C>A	upstream_gene	N/A	ENSP00000546190.1
RAB25	ENST00000921090.1		c.-372C>A	upstream_gene	N/A	ENSP00000591149.1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91531

AN:

151892

Hom.:

32070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.654

GnomAD4 exome

AF:

0.707

AC:

15262

AN:

21588

Hom.:

5879

AF XY:

0.703

AC XY:

8081

AN XY:

11488

show subpopulations

African (AFR)

AF:

0.259

AC:

145

AN:

560

American (AMR)

AF:

0.735

AC:

645

AN:

878

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

453

AN:

612

East Asian (EAS)

AF:

0.172

AC:

243

AN:

1412

South Asian (SAS)

AF:

0.633

AC:

1197

AN:

1892

European-Finnish (FIN)

AF:

0.736

AC:

624

AN:

848

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.781

AC:

10989

AN:

14068

Other (OTH)

AF:

0.726

AC:

896

AN:

1234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

183

366

549

732

915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.602

AC:

91522

AN:

152012

Hom.:

32068

Cov.:

AF XY:

0.601

AC XY:

44651

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.261

AC:

10824

AN:

41444

American (AMR)

AF:

0.705

AC:

10773

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

2576

AN:

3468

East Asian (EAS)

AF:

0.145

AC:

748

AN:

5170

South Asian (SAS)

AF:

0.613

AC:

2954

AN:

4816

European-Finnish (FIN)

AF:

0.755

AC:

7986

AN:

10576

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.784

AC:

53249

AN:

67956

Other (OTH)

AF:

0.652

AC:

1370

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1424

2848

4272

5696

7120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.717

Hom.:

22345

Bravo

AF:

0.584

Asia WGS

AF:

0.398

AC:

1386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.52

(source)

DANN

Benign

0.82

PhyloP100

0.37

PromoterAI

-0.047

Neutral

(source)

Splicing

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