dbSNP rs1554844950: RBM20:p.Ala1208_Asp1209insGluGluGlyLeuLysGluThrGluGlyAla (chr10-110835884-T-TGGCCGAGGAGGGCCTCAAGGAGACCGAGGG) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_001134363.3(RBM20):c.3594_3623dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC(p.Ala1208_Asp1209insGluGluGlyLeuLysGluThrGluGlyAla) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RBM20
NM_001134363.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001134363.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3 link	c.3594_3623dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC	p.Ala1208_Asp1209insGluGluGlyLeuLysGluThrGluGlyAla	disruptive_inframe_insertion	Exon 14 of 14	ENST00000369519.4	NP_001127835.2	Q5T481
RBM20	XM_017016103.3 link	c.3429_3458dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC	p.Ala1153_Asp1154insGluGluGlyLeuLysGluThrGluGlyAla	disruptive_inframe_insertion	Exon 14 of 14		XP_016871592.1
RBM20	XM_017016104.3 link	c.3210_3239dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC	p.Ala1080_Asp1081insGluGluGlyLeuLysGluThrGluGlyAla	disruptive_inframe_insertion	Exon 14 of 14		XP_016871593.1
RBM20	XM_047425116.1 link	c.3210_3239dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC	p.Ala1080_Asp1081insGluGluGlyLeuLysGluThrGluGlyAla	disruptive_inframe_insertion	Exon 14 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM20	ENST00000369519.4 link	c.3594_3623dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC	p.Ala1208_Asp1209insGluGluGlyLeuLysGluThrGluGlyAla	disruptive_inframe_insertion	Exon 14 of 14	1	NM_001134363.3	ENSP00000358532.3	Q5T481
RBM20	ENST00000465774.2 link	n.535_564dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC		non_coding_transcript_exon_variant	Exon 2 of 2	4
RBM20	ENST00000480343.2 link	n.227_256dupCGAGGAGGGCCTCAAGGAGACCGAGGGGGC		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1DD

Uncertain:1

Dec 18, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.3594_3623dup, results in the insertion of 10 amino acid(s) of the RBM20 protein (p.Glu1199_Ala1208dup), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 470614). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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