Genetic Variant NM_001134363.3:c.153G>C (chr10-110644607-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_001134363.3(RBM20):c.153G>C(p.Pro51Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P51P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM20
NM_001134363.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=1.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.153G>C	p.Pro51Pro	synonymous_variant	Exon 1 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3 link	c.26+1167G>C		intron_variant	Intron 1 of 13		XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4 link	c.153G>C	p.Pro51Pro	synonymous_variant	Exon 1 of 14	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1 link	c.153G>C	p.Pro51Pro	synonymous_variant	Exon 1 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes

AF:

0.0000481

AC:

AN:

145508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000497

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000450

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00150

AC:

1411

AN:

939818

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

660

AN XY:

472454

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00214

AC:

AN:

19636

American (AMR)

AF:

0.000141

AC:

AN:

28438

Ashkenazi Jewish (ASJ)

AF:

0.000916

AC:

AN:

17460

East Asian (EAS)

AF:

0.000491

AC:

AN:

22400

South Asian (SAS)

AF:

0.000391

AC:

AN:

69070

European-Finnish (FIN)

AF:

0.0000737

AC:

AN:

27142

Middle Eastern (MID)

AF:

0.00131

AC:

AN:

3050

European-Non Finnish (NFE)

AF:

0.00175

AC:

1253

AN:

714464

Other (OTH)

AF:

0.00136

AC:

AN:

38158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.243

Heterozygous variant carriers

219

438

656

875

1094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

198

264

330

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000481

AC:

AN:

145652

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

71046

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000496

AC:

AN:

40324

American (AMR)

AF:

0.00

AC:

AN:

14762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.000451

AC:

AN:

4434

South Asian (SAS)

AF:

0.00

AC:

AN:

4092

European-Finnish (FIN)

AF:

0.000216

AC:

AN:

9258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66178

Other (OTH)

AF:

0.00

AC:

AN:

2060

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.239

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.7

(source)

DANN

Benign

0.87

PhyloP100

1.6

PromoterAI

-0.086

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over