10-110810372-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001134363.3(RBM20):c.1801-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,549,418 control chromosomes in the GnomAD database, including 876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 82 hom., cov: 32)

Exomes 𝑓: 0.027 ( 794 hom. )

Consequence

RBM20
NM_001134363.3 intron

Scores

Splicing: ADA: 0.00003465

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.296

Publications

5 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), Ambry Genetics, G2P
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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 10-110810372-G-C is Benign according to our data. Variant chr10-110810372-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.1801-11G>C	intron_variant	Intron 7 of 13	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.1636-11G>C	intron_variant	Intron 7 of 13		XP_016871592.1
RBM20	XM_017016104.3 link	c.1417-11G>C	intron_variant	Intron 7 of 13		XP_016871593.1
RBM20	XM_047425116.1 link	c.1417-11G>C	intron_variant	Intron 7 of 13		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4 link	c.1801-11G>C		intron_variant	Intron 7 of 13	1	NM_001134363.3	ENSP00000358532.3		Q5T481
RBM20	ENST00000718239.1 link	c.1801-11G>C		intron_variant	Intron 7 of 13			ENSP00000520684.1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4033

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.0267

Gnomad SAS

AF:

0.0995

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0350

GnomAD2 exomes

AF:

0.0350

AC:

5478

AN:

156494

AF XY:

0.0388

show subpopulations

Gnomad AFR exome

AF:

0.0280

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.0288

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0232

Gnomad OTH exome

AF:

0.0314

GnomAD4 exome

AF:

0.0270

AC:

37697

AN:

1397150

Hom.:

794

Cov.:

AF XY:

0.0291

AC XY:

20034

AN XY:

689216

show subpopulations

African (AFR)

AF:

0.0256

AC:

808

AN:

31558

American (AMR)

AF:

0.0182

AC:

649

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.0226

AC:

569

AN:

25162

East Asian (EAS)

AF:

0.0246

AC:

879

AN:

35708

South Asian (SAS)

AF:

0.0941

AC:

7445

AN:

79096

European-Finnish (FIN)

AF:

0.0379

AC:

1867

AN:

49224

Middle Eastern (MID)

AF:

0.0450

AC:

256

AN:

5694

European-Non Finnish (NFE)

AF:

0.0217

AC:

23427

AN:

1077106

Other (OTH)

AF:

0.0310

AC:

1797

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1594

3187

4781

6374

7968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

964

1928

2892

3856

4820

<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:

0.0265

AC:

4042

AN:

152268

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

2103

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0264

AC:

1096

AN:

41534

American (AMR)

AF:

0.0214

AC:

327

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3472

East Asian (EAS)

AF:

0.0266

AC:

138

AN:

5186

South Asian (SAS)

AF:

0.0998

AC:

481

AN:

4818

European-Finnish (FIN)

AF:

0.0341

AC:

362

AN:

10610

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0215

AC:

1461

AN:

68030

Other (OTH)

AF:

0.0403

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

198

397

595

794

992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0151

Hom.:

Bravo

AF:

0.0243

Asia WGS

AF:

0.100

AC:

349

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Oct 18, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 17, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1801-11G>C in intron 7 of RBM20: This variant is not expected to have clinical s ignificance because it has been identified in 2.6% (67/2532) of European America n chromosomes and 3.3% (23/702) of African American chromosomes from a broad pop ulation by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/ ; dbSNP rs12572941) -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated cardiomyopathy 1DD

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.024

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over