rs1954179

chr10-110692374-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134363.3(RBM20):c.191+47729A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,024 control chromosomes in the GnomAD database, including 7,773 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 0.31 (7773 hom., cov: 33)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.191+47729A>G		intron_variant		ENST00000369519.4
RBM20	XM_017016103.3	c.26+48934A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.191+47729A>G		intron_variant		1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47258 AN: 151906 Hom.: 7769 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.311 AC: 47289 AN: 152024 Hom.: 7773 Cov.: 33 AF XY: 0.307 AC XY: 22781 AN XY: 74304

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.328

Alfa AF: 0.333 Hom.: 3917

Bravo AF: 0.302

Asia WGS AF: 0.128 AC: 447 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.9
Dann	Benign	0.69

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: rs1954179; hg19: chr10-112452132;