10-110835961-G-C

Position:

chr10-110835961-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134363.3(RBM20):c.3667G>C(p.Glu1223Gln) variant causes a missense change. The variant allele was found at a frequency of 0.828 in 1,259,556 control chromosomes in the GnomAD database, including 437,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 44456 hom., cov: 33)

Exomes 𝑓: 0.84 ( 392666 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 4.12

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:

RBM20 (HGNC:):

RBM20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.3003877E-7).

BP6

Variant 10-110835961-G-C is Benign according to our data. Variant chr10-110835961-G-C is described in ClinVar as [Benign]. Clinvar id is 44016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110835961-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3 linkuse as main transcript	c.3667G>C	p.Glu1223Gln	missense_variant	14/14	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 linkuse as main transcript	c.3502G>C	p.Glu1168Gln	missense_variant	14/14		XP_016871592.1
RBM20	XM_017016104.3 linkuse as main transcript	c.3283G>C	p.Glu1095Gln	missense_variant	14/14		XP_016871593.1
RBM20	XM_047425116.1 linkuse as main transcript	c.3283G>C	p.Glu1095Gln	missense_variant	14/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM20	ENST00000369519.4 linkuse as main transcript	c.3667G>C	p.Glu1223Gln	missense_variant	14/14	1	NM_001134363.3	ENSP00000358532.3	Q5T481
RBM20	ENST00000465774.2 linkuse as main transcript	n.608G>C		non_coding_transcript_exon_variant	2/2	4
RBM20	ENST00000480343.2 linkuse as main transcript	n.300G>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113647

AN:

152112

Hom.:

44459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.772

GnomAD3 exomes

AF:

0.803

AC:

110677

AN:

137800

Hom.:

45185

AF XY:

0.802

AC XY:

58861

AN XY:

73424

show subpopulations

Gnomad AFR exome

AF:

0.469

Gnomad AMR exome

AF:

0.785

Gnomad ASJ exome

AF:

0.846

Gnomad EAS exome

AF:

0.801

Gnomad SAS exome

AF:

0.719

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.867

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.839

AC:

928605

AN:

1107326

Hom.:

392666

Cov.:

AF XY:

0.836

AC XY:

465058

AN XY:

556506

show subpopulations

Gnomad4 AFR exome

AF:

0.471

Gnomad4 AMR exome

AF:

0.780

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.718

Gnomad4 FIN exome

AF:

0.864

Gnomad4 NFE exome

AF:

0.866

Gnomad4 OTH exome

AF:

0.809

GnomAD4 genome

AF:

0.747

AC:

113681

AN:

152230

Hom.:

44456

Cov.:

AF XY:

0.746

AC XY:

55558

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.791

Gnomad4 ASJ

AF:

0.850

Gnomad4 EAS

AF:

0.789

Gnomad4 SAS

AF:

0.719

Gnomad4 FIN

AF:

0.862

Gnomad4 NFE

AF:

0.867

Gnomad4 OTH

AF:

0.769

Alfa

AF:

0.830

Hom.:

16732

Bravo

AF:

0.729

TwinsUK

AF:

0.876

AC:

3249

ALSPAC

AF:

0.859

AC:

3312

ESP6500AA

AF:

0.496

AC:

687

ESP6500EA

AF:

0.872

AC:

2776

ExAC

AF:

0.741

AC:

16396

Asia WGS

AF:

0.704

AC:

2450

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 13, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 16, 2011	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 31, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Dilated cardiomyopathy 1DD

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Primary dilated cardiomyopathy

Benign:1

Benign, no assertion criteria provided

clinical testing

Cohesion Phenomics

Sep 27, 2022

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

9.3e-7

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.72

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

Sift4G

Benign

0.087

Vest4

0.032

ClinPred

0.014

GERP RS

5.2

gMVP

0.30

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

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