rs187915202

Variant names:

• chr10-110820191-A-G
• rs187915202
• NM_001134363.3:c.2655+15A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001134363.3(RBM20):​c.2655+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 1,525,998 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (31 hom.)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:10
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-110820191-A-G is Benign according to our data. Variant chr10-110820191-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43993.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=5, Uncertain_significance=1}. Variant chr10-110820191-A-G is described in Lovd as [Benign]. Variant chr10-110820191-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00423 (645/152334) while in subpopulation NFE AF= 0.00685 (466/68032). AF 95% confidence interval is 0.00634. There are 0 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 645 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.2655+15A>G		intron_variant	Intron 10 of 13	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.2490+15A>G		intron_variant	Intron 10 of 13		XP_016871592.1
RBM20	XM_017016104.3	c.2271+15A>G		intron_variant	Intron 10 of 13		XP_016871593.1
RBM20	XM_047425116.1	c.2271+15A>G		intron_variant	Intron 10 of 13		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.2655+15A>G		intron_variant	Intron 10 of 13	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00685

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00403 AC: 628 AN: 155940 Hom.: 3 AF XY: 0.00381 AC XY: 315 AN XY: 82688

Gnomad AFR exome AF: 0.00139

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.000353

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.00570

Gnomad NFE exome AF: 0.00655

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00589 AC: 8089 AN: 1373664 Hom.: 31 Cov.: 24 AF XY: 0.00571 AC XY: 3881 AN XY: 679186

Gnomad4 AFR exome AF: 0.00109

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.000600

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.00592

Gnomad4 NFE exome AF: 0.00686

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.00423 AC: 645 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74492

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.00685

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00509 Hom.: 0

Bravo AF: 0.00377

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:10

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Benign:6

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 17, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2655+15A>G in intron 10 of RBM20: This variant is not expected to have clinical significance because it has been identified in 0.3% (10/3182) of European Americ an chromosomes and 0.15% (2/1384) of African American chromosomes by the NHLBI E xome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs187915202). 2655+15A>G in intron 10 of RBM20: rs187915202; allele frequency = 0.3 (10/3182 ) ** -

Feb 20, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1DD Uncertain:1 Benign:2

Sep 15, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RBM20: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs187915202; hg19: chr10-112579949;