10-110780972-C-T

Variant names:

• chr10-110780972-C-T
• rs727504930
• NM_001134363.3:c.363C>T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001134363.3(RBM20):​c.363C>T​(p.Asn121Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,551,638 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: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.412

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-110780972-C-T is Benign according to our data. Variant chr10-110780972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 179531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-110780972-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.412 with no splicing effect.
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.363C>T	p.Asn121Asn	synonymous_variant	Exon 2 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.198C>T	p.Asn66Asn	synonymous_variant	Exon 2 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.-22C>T		5_prime_UTR_variant	Exon 2 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.-22C>T		5_prime_UTR_variant	Exon 2 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.363C>T	p.Asn121Asn	synonymous_variant	Exon 2 of 14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000643 AC: 9 AN: 1399448 Hom.: 0 Cov.: 32 AF XY: 0.00000724 AC XY: 5 AN XY: 690226

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74346

Gnomad4 AFR AF: 0.00

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: 0.0000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 06, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asn121Asn in exon 2 of RBM20: It is not expected to have clinical significance b ecause it does not alter an amino acid residue and is not located within the spl ice consensus sequence. Asn121Asn in exon 2 of RBM20 (allele frequency = n/a) -

Dec 09, 2015

GeneDx

Significance: Likely 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. -

Dilated cardiomyopathy 1DD Benign:1

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Mar 13, 2023

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	-0.53
CADD	Benign	6.6
DANN	Benign	0.56

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: rs727504930; hg19: chr10-112540730;