rs867232627

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001134363.3(RBM20):c.3649G>A(p.Gly1217Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,400,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 5.67

Publications

0 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 -9 ACMG points.

BP6

Variant 10-110835943-G-A is Benign according to our data. Variant chr10-110835943-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 470615.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000216 (27/1248068) while in subpopulation EAS AF = 0.000694 (24/34584). AF 95% confidence interval is 0.000478. There are 0 homozygotes in GnomAdExome4. There are 14 alleles in the male GnomAdExome4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.3649G>A	p.Gly1217Arg	missense_variant	Exon 14 of 14	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.3484G>A	p.Gly1162Arg	missense_variant	Exon 14 of 14		XP_016871592.1
RBM20	XM_017016104.3 link	c.3265G>A	p.Gly1089Arg	missense_variant	Exon 14 of 14		XP_016871593.1
RBM20	XM_047425116.1 link	c.3265G>A	p.Gly1089Arg	missense_variant	Exon 14 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM20	ENST00000369519.4 link	c.3649G>A	p.Gly1217Arg	missense_variant	Exon 14 of 14	1	NM_001134363.3	ENSP00000358532.3	Q5T481
RBM20	ENST00000718239.1 link	c.3649G>A	p.Gly1217Arg	missense_variant	Exon 14 of 14			ENSP00000520684.1
RBM20	ENST00000465774.2 link	n.590G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4
RBM20	ENST00000480343.2 link	n.282G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

143200

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000216

AC:

AN:

1248068

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

622608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28030

American (AMR)

AF:

0.00

AC:

AN:

34160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24032

East Asian (EAS)

AF:

0.000694

AC:

AN:

34584

South Asian (SAS)

AF:

0.00

AC:

AN:

75174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5386

European-Non Finnish (NFE)

AF:

0.00000212

AC:

AN:

944710

Other (OTH)

AF:

0.0000189

AC:

AN:

52884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000264

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:2

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 17, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.G1217R variant (also known as c.3649G>A), located in coding exon 14 of the RBM20 gene, results from a G to A substitution at nucleotide position 3649. The glycine at codon 1217 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Dilated cardiomyopathy 1DD

Uncertain:1Benign:1

Jan 12, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

M_CAP

Pathogenic

0.51

MetaRNN

Uncertain

0.73

MetaSVM

Pathogenic

1.1

PhyloP100

5.7

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.57

MutPred

0.20

Gain of MoRF binding (P = 0.013);

MVP

0.77

ClinPred

0.97

GERP RS

5.0

gMVP

0.48

Mutation Taster

=61/39

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

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rs867232627

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