rs11195299

Positions:

• chr10-110742384-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.192-38417G>A		intron_variant		ENST00000369519.4
RBM20	XM_017016103.3	c.27-38417G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.192-38417G>A		intron_variant		1	NM_001134363.3	P1

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

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.0558

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.0877

Alfa AF: 0.0917 Hom.: 354

Bravo AF: 0.0776

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.42

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