10-110831121-C-T

Variant names:

Variant summary

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

The NM_001134363.3(RBM20):c.3512C>T(p.Thr1171Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,551,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T1171K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.66

Publications

2 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 -9 ACMG points.

BP6

Variant 10-110831121-C-T is Benign according to our data. Variant chr10-110831121-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 470611.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000118 (18/152162) while in subpopulation AFR AF = 0.000338 (14/41426). AF 95% confidence interval is 0.000204. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 18 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.3512C>T	p.Thr1171Met	missense	Exon 13 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.3512C>T	p.Thr1171Met	missense	Exon 13 of 14	ENSP00000358532.3	Q5T481
RBM20	ENST00000961386.1		c.3542C>T	p.Thr1181Met	missense	Exon 13 of 14	ENSP00000631445.1
RBM20	ENST00000718239.1		c.3512C>T	p.Thr1171Met	missense	Exon 13 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000585

AC:

AN:

153956

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000250

AC:

AN:

1399284

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

690150

show subpopulations

African (AFR)

AF:

0.000411

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.000112

AC:

AN:

35736

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1078888

Other (OTH)

AF:

0.0000172

AC:

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.000118

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41426

American (AMR)

AF:

0.0000654

AC:

AN:

15280

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:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000124

Hom.:

Bravo

AF:

0.000147

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

Dilated cardiomyopathy 1DD (2)

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.58

MetaSVM

Uncertain

0.17

PhyloP100

4.7

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Vest4

0.59

MVP

0.76

ClinPred

0.50

GERP RS

5.4

gMVP

0.45

Mutation Taster

=72/28

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