rs77110978

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001134363.3(RBM20):c.3331G>A(p.Val1111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,503,670 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1111L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00020 ( 4 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.38

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064791143).

BP6

Variant 10-110823494-G-A is Benign according to our data. Variant chr10-110823494-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 411648.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00011 (15/136784) while in subpopulation EAS AF = 0.00278 (13/4676). AF 95% confidence interval is 0.00164. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 15 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	NM_001134363.3	MANE Select	c.3331G>A	p.Val1111Met	missense	Exon 12 of 14	NP_001127835.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RBM20	ENST00000369519.4	TSL:1 MANE Select	c.3331G>A	p.Val1111Met	missense	Exon 12 of 14	ENSP00000358532.3
RBM20	ENST00000718239.1		c.3331G>A	p.Val1111Met	missense	Exon 12 of 14	ENSP00000520684.1
RBM20	ENST00000471172.1	TSL:5	n.-94G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000110

AC:

AN:

136738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000838

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00277

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000468

AC:

AN:

149530

AF XY:

0.0000506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000195

AC:

267

AN:

1366886

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

130

AN XY:

673094

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30016

American (AMR)

AF:

0.0000298

AC:

AN:

33590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24436

East Asian (EAS)

AF:

0.00749

AC:

256

AN:

34192

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.00000472

AC:

AN:

1058708

Other (OTH)

AF:

0.0000534

AC:

AN:

56130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000110

AC:

AN:

136784

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

65126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35798

American (AMR)

AF:

0.0000837

AC:

AN:

11942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00278

AC:

AN:

4676

South Asian (SAS)

AF:

0.00

AC:

AN:

4332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66018

Other (OTH)

AF:

0.00

AC:

AN:

1870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

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:

0.000127

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000426

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Dilated cardiomyopathy 1DD (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.013

(source)

DANN

Benign

0.77

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0032

M_CAP

Benign

0.012

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.95

PhyloP100

-4.4

PrimateAI

Benign

0.20

PROVEAN

Benign

0.17

REVEL

Benign

0.21

Sift

Benign

0.81

Sift4G

Benign

0.23

Vest4

0.058

MVP

0.15

ClinPred

0.021

GERP RS

-12

gMVP

0.20

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over