rs375355193

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_001134363.3(RBM20):c.3004C>G(p.Leu1002Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,551,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 1.60

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), 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08574352).

BP6

Variant 10-110821623-C-G is Benign according to our data. Variant chr10-110821623-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 179029.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000131 (20/152216) while in subpopulation AFR AF = 0.000483 (20/41442). AF 95% confidence interval is 0.00032. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 20 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.3004C>G	p.Leu1002Val	missense	Exon 11 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.3004C>G	p.Leu1002Val	missense	Exon 11 of 14	ENSP00000358532.3	Q5T481
RBM20	ENST00000961386.1		c.3034C>G	p.Leu1012Val	missense	Exon 11 of 14	ENSP00000631445.1
RBM20	ENST00000718239.1		c.3004C>G	p.Leu1002Val	missense	Exon 11 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

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:

0.0000128

AC:

AN:

156732

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000250

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:

0.0000157

AC:

AN:

1399340

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

690128

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

31596

American (AMR)

AF:

0.0000560

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078866

Other (OTH)

AF:

0.0000345

AC:

AN:

58014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000483

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

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:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.00

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

ClinVar submissions

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

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.042

MetaRNN

Benign

0.086

MetaSVM

Uncertain

0.18

PhyloP100

1.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.0

REVEL

Benign

0.21

Sift

Benign

0.10

Sift4G

Benign

0.61

Vest4

0.086

MVP

0.40

ClinPred

0.19

GERP RS

4.0

gMVP

0.17

Mutation Taster

=88/12

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