rs11195299

Variant names:

• chr10-110742384-G-A
• rs11195299
• NM_001134363.3:c.192-38417G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134363.3(RBM20):​c.192-38417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 152,126 control chromosomes in the GnomAD database, including 943 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.081 (943 hom., cov: 32)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1DD

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	NM_001134363.3	MANE Select	c.192-38417G>A		intron	N/A	NP_001127835.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.192-38417G>A		intron	N/A	ENSP00000358532.3
	RBM20	ENST00000718239.1		c.192-38417G>A		intron	N/A	ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12331 AN: 152008 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0891

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0810 AC: 12315 AN: 152126 Hom.: 943 Cov.: 32 AF XY: 0.0838 AC XY: 6230 AN XY: 74360

African (AFR) AF: 0.0218 AC: 904 AN: 41548

American (AMR) AF: 0.0558 AC: 853 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2170 AN: 5150

South Asian (SAS) AF: 0.124 AC: 595 AN: 4812

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6044 AN: 67956

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0917 Hom.: 387

Bravo AF: 0.0776

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11195299; hg19: chr10-112502142; COSMIC: COSV65707610;