Genetic Variant NM_001278639.2:c.670+294T>G (chr22-20125730-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001278639.2(RANBP1):c.670+294T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,174,684 control chromosomes in the GnomAD database, including 44,297 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 0.27 ( 5721 hom., cov: 34)

Exomes 𝑓: 0.27 ( 38576 hom. )

Consequence

RANBP1
NM_001278639.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

7 publications found

Variant links:

Genes affected

RANBP1 (HGNC:9847): (RAN binding protein 1) This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RANBP1 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=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278639.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RANBP1	NM_001278639.2	MANE Select	c.670+294T>G	intron	N/A	NP_001265568.1
RANBP1	NM_002882.4		c.439+294T>G	intron	N/A	NP_002873.1
RANBP1	NM_001278640.2		c.439+294T>G	intron	N/A	NP_001265569.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RANBP1	ENST00000430524.6	TSL:3 MANE Select	c.670+294T>G	intron	N/A	ENSP00000401564.2
RANBP1	ENST00000331821.8	TSL:1	c.439+294T>G	intron	N/A	ENSP00000327583.3
RANBP1	ENST00000402752.5	TSL:1	c.439+294T>G	intron	N/A	ENSP00000384925.1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41279

AN:

152116

Hom.:

5717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.273

AC:

278768

AN:

1022448

Hom.:

38576

AF XY:

0.274

AC XY:

135820

AN XY:

496242

show subpopulations

African (AFR)

AF:

0.273

AC:

6065

AN:

22228

American (AMR)

AF:

0.233

AC:

3417

AN:

14676

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

4357

AN:

13104

East Asian (EAS)

AF:

0.159

AC:

3053

AN:

19256

South Asian (SAS)

AF:

0.307

AC:

17873

AN:

58292

European-Finnish (FIN)

AF:

0.298

AC:

4640

AN:

15594

Middle Eastern (MID)

AF:

0.258

AC:

680

AN:

2640

European-Non Finnish (NFE)

AF:

0.272

AC:

227738

AN:

836590

Other (OTH)

AF:

0.273

AC:

10945

AN:

40068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

9870

19740

29609

39479

49349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8488

16976

25464

33952

42440

<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:

0.271

AC:

41310

AN:

152236

Hom.:

5721

Cov.:

AF XY:

0.272

AC XY:

20228

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.280

AC:

11652

AN:

41558

American (AMR)

AF:

0.239

AC:

3655

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1154

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

795

AN:

5176

South Asian (SAS)

AF:

0.291

AC:

1404

AN:

4830

European-Finnish (FIN)

AF:

0.301

AC:

3180

AN:

10578

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18513

AN:

68006

Other (OTH)

AF:

0.285

AC:

603

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1601

3201

4802

6402

8003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.265

Hom.:

1549

Bravo

AF:

0.268

Asia WGS

AF:

0.217

AC:

754

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.24

(source)

DANN

Benign

0.29

PhyloP100

-1.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over