chr10-110644449-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001134363.3(RBM20):​c.-6C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,483,238 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

RBM20
NM_001134363.3 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.374
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 10-110644449-C-T is Benign according to our data. Variant chr10-110644449-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 43962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 214 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RBM20NM_001134363.3 linkuse as main transcriptc.-6C>T 5_prime_UTR_variant 1/14 ENST00000369519.4
RBM20XM_017016103.3 linkuse as main transcriptc.26+1009C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RBM20ENST00000369519.4 linkuse as main transcriptc.-6C>T 5_prime_UTR_variant 1/141 NM_001134363.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
33
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000694
AC:
6
AN:
86428
Hom.:
0
AF XY:
0.0000818
AC XY:
4
AN XY:
48926
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000190
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000161
AC:
214
AN:
1331056
Hom.:
1
Cov.:
31
AF XY:
0.000176
AC XY:
115
AN XY:
655006
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:
0.000202
Gnomad4 OTH exome
AF:
0.0000181
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJul 31, 2012-6C>T in the 5' UTR of RBM20: This variant is located in the 5' UTR and varian ts in regulatory regions could have an effect on transcriptional or translationa l efficiency. However, no variants in this region of RBM20 have been found to be pathogenic in individuals with cardiomyopathy. Therefore, this variant is not e xpected to have clinical significance. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 27, 2022See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
14
DANN
Benign
0.92

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: rs397516589; hg19: chr10-112404207; API