rs116908219

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001134363.3(RBM20):c.3373G>A(p.Glu1125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,545,238 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0038 ( 20 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 3.33

Publications

11 publications found

Variant links:

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

RBM20 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1DD
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RBM20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007486701).

BP6

Variant 10-110823536-G-A is Benign according to our data. Variant chr10-110823536-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00326 (484/148400) while in subpopulation NFE AF = 0.00457 (309/67630). AF 95% confidence interval is 0.00415. There are 0 homozygotes in GnomAd4. There are 227 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 484 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134363.3. 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
	RBM20	NM_001134363.3	MANE Select	c.3373G>A	p.Glu1125Lys	missense	Exon 12 of 14	NP_001127835.2	Q5T481

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM20	ENST00000369519.4	TSL:1 MANE Select	c.3373G>A	p.Glu1125Lys	missense	Exon 12 of 14	ENSP00000358532.3	Q5T481
RBM20	ENST00000961386.1		c.3403G>A	p.Glu1135Lys	missense	Exon 12 of 14	ENSP00000631445.1
RBM20	ENST00000718239.1		c.3373G>A	p.Glu1125Lys	missense	Exon 12 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

484

AN:

148290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000782

Gnomad AMI

AF:

0.00664

Gnomad AMR

AF:

0.00376

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000426

Gnomad FIN

AF:

0.00121

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00295

GnomAD2 exomes

AF:

0.00362

AC:

567

AN:

156520

AF XY:

0.00354

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00509

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00381

AC:

5325

AN:

1396838

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

2630

AN XY:

688914

show subpopulations

African (AFR)

AF:

0.000606

AC:

AN:

31332

American (AMR)

AF:

0.00202

AC:

AN:

35604

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

450

AN:

25110

East Asian (EAS)

AF:

0.00

AC:

AN:

35644

South Asian (SAS)

AF:

0.00105

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00167

AC:

AN:

49098

Middle Eastern (MID)

AF:

0.00458

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00403

AC:

4345

AN:

1077394

Other (OTH)

AF:

0.00429

AC:

248

AN:

57784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

264

528

791

1055

1319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.00326

AC:

484

AN:

148400

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

227

AN XY:

72256

show subpopulations

African (AFR)

AF:

0.000780

AC:

AN:

39768

American (AMR)

AF:

0.00375

AC:

AN:

14654

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5014

South Asian (SAS)

AF:

0.000426

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.00121

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00457

AC:

309

AN:

67630

Other (OTH)

AF:

0.00292

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00457

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00534

AC:

ExAC

AF:

0.00340

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Dilated cardiomyopathy 1DD (4)

not provided (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Long QT syndrome;C0349788:Arrhythmogenic right ventricular cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.010

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.50

PhyloP100

3.3

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.32

Sift

Benign

0.037

Sift4G

Benign

0.073

Vest4

0.29

MVP

0.71

ClinPred

0.011

GERP RS

6.2

gMVP

0.48

Mutation Taster

=89/11

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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