10-110780834-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001134363.3(RBM20):​c.225G>C​(p.Ser75Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,386,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 10-110780834-G-C is Benign according to our data. Variant chr10-110780834-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1788597.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.79 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM20NM_001134363.3 linkc.225G>C p.Ser75Ser synonymous_variant Exon 2 of 14 ENST00000369519.4 NP_001127835.2 Q5T481
RBM20XM_017016103.3 linkc.60G>C p.Ser20Ser synonymous_variant Exon 2 of 14 XP_016871592.1
RBM20XM_017016104.3 linkc.-160G>C 5_prime_UTR_variant Exon 2 of 14 XP_016871593.1
RBM20XM_047425116.1 linkc.-160G>C 5_prime_UTR_variant Exon 2 of 14 XP_047281072.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM20ENST00000369519.4 linkc.225G>C p.Ser75Ser synonymous_variant Exon 2 of 14 1 NM_001134363.3 ENSP00000358532.3 Q5T481

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000289
AC:
4
AN:
1386402
Hom.:
0
Cov.:
32
AF XY:
0.00000440
AC XY:
3
AN XY:
681564
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000374
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cardiovascular phenotype Benign:1
Sep 11, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely 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
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.072
DANN
Benign
0.48

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.

Other links and lift over

dbSNP: rs1170141703; hg19: chr10-112540592; API