rs1954179

Variant names:

• chr10-110692374-A-G
• rs1954179
• NM_001134363.3:c.191+47729A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.9).
• 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 rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.191+47729A>G		intron_variant	Intron 1 of 13	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+48934A>G		intron_variant	Intron 1 of 13		XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.191+47729A>G		intron_variant	Intron 1 of 13	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.191+47729A>G		intron_variant	Intron 1 of 13			ENSP00000520684.1

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

African (AFR) AF: 0.295 AC: 12227 AN: 41474

American (AMR) AF: 0.260 AC: 3980 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5188

South Asian (SAS) AF: 0.196 AC: 942 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4007 AN: 10528

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23856 AN: 67944

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.334 Hom.: 4397

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
PhyloP100		-0.24
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: rs1954179; hg19: chr10-112452132;