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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB25	NM_020387.4 link	c.-372C>A		upstream_gene_variant		ENST00000361084.10	NP_065120.2
RAB25	NR_133653.2 link	n.-131C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
RAB25	ENST00000361084.10 link	c.-372C>A	upstream_gene_variant	1	NM_020387.4	ENSP00000354376.5
RAB25	ENST00000463614.1 link	n.-160C>A	upstream_gene_variant	2
RAB25	ENST00000487325.5 link	n.-177C>A	upstream_gene_variant	2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over