dbSNP rs376936285: RBM20:p.Pro50Pro (chr10-110644604-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001134363.3(RBM20):c.150A>C(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P50P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM20
NM_001134363.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.80

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-110644604-A-C is Benign according to our data. Variant chr10-110644604-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 518221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110644604-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.8 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.150A>C	p.Pro50Pro	synonymous_variant	Exon 1 of 14	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.26+1164A>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.150A>C	p.Pro50Pro	synonymous_variant	Exon 1 of 14	1	NM_001134363.3	ENSP00000358532.3		Q5T481

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138430

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000258

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000572

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000126

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000603

AC:

604

AN:

1002316

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

294

AN XY:

500576

show subpopulations

Gnomad4 AFR exome

AF:

0.000739

Gnomad4 AMR exome

AF:

0.0000357

Gnomad4 ASJ exome

AF:

0.000962

Gnomad4 EAS exome

AF:

0.000276

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.000670

Gnomad4 OTH exome

AF:

0.000614

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000152

AC:

AN:

138582

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

67362

show subpopulations

Gnomad4 AFR

AF:

0.0000790

Gnomad4 AMR

AF:

0.000282

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000258

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000572

Gnomad4 NFE

AF:

0.000126

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RBM20: BP4, BP7 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1DD

Benign:2

Aug 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.083

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over