rs376936285

Positions:

• chr10-110644604-A-C
• chr10-110644604-A-G
• chr10-110644604-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.80

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=-0.79).
• 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/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.150A>C	p.Pro50Pro	synonymous_variant	1/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+1164A>C		intron_variant			XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.150A>C	p.Pro50Pro	synonymous_variant	1/14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 21 AN: 138430 Hom.: 0 Cov.: 32 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.: 0 Cov.: 35 AF XY: 0.000587 AC XY: 294 AN XY: 500576

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: 21 AN: 138582 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 9 AN XY: 67362

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

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	RBM20: BP4, BP7 -

Dilated cardiomyopathy 1DD Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 15, 2022	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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

Other links and lift over

dbSNP: rs376936285; hg19: chr10-112404362;