rs886038858

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001134363.3(RBM20):c.3023G>A(p.Arg1008Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000058 in 1,551,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1008W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520

Publications

4 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035711825).

BP6

Variant 10-110821642-G-A is Benign according to our data. Variant chr10-110821642-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000629 (88/1399438) while in subpopulation MID AF = 0.000351 (2/5700). AF 95% confidence interval is 0.0000634. There are 0 homozygotes in GnomAdExome4. There are 44 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.3023G>A	p.Arg1008Gln	missense_variant	Exon 11 of 14	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.2858G>A	p.Arg953Gln	missense_variant	Exon 11 of 14		XP_016871592.1
RBM20	XM_017016104.3 link	c.2639G>A	p.Arg880Gln	missense_variant	Exon 11 of 14		XP_016871593.1
RBM20	XM_047425116.1 link	c.2639G>A	p.Arg880Gln	missense_variant	Exon 11 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4 link	c.3023G>A	p.Arg1008Gln	missense_variant	Exon 11 of 14	1	NM_001134363.3	ENSP00000358532.3		Q5T481
RBM20	ENST00000718239.1 link	c.3023G>A	p.Arg1008Gln	missense_variant	Exon 11 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

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:

0.0000192

AC:

AN:

156598

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000330

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000629

AC:

AN:

1399438

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

690216

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31598

American (AMR)

AF:

0.0000280

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000769

AC:

AN:

1078968

Other (OTH)

AF:

0.00

AC:

AN:

58014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1DD

Benign:1

Jan 22, 2025

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

0.064

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.40

M_CAP

Benign

0.021

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.79

PhyloP100

0.052

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.010

REVEL

Benign

0.23

Sift

Benign

0.71

Sift4G

Benign

0.54

Vest4

0.049

MutPred

0.098

Gain of relative solvent accessibility (P = 0.09);

MVP

0.29

ClinPred

0.093

GERP RS

-0.31

gMVP

0.098

Mutation Taster

=93/7

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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rs886038858

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