NM_001134363.3:c.191+23046C>T

Variant names:

• chr10-110667691-C-T
• rs7082195
• NM_001134363.3:c.191+23046C>T

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+23046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,106 control chromosomes in the GnomAD database, including 1,637 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 0.15 (1637 hom., cov: 32)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.191+23046C>T		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.191+23046C>T		intron	N/A	ENSP00000358532.3
	RBM20	ENST00000961386.1		c.191+23046C>T		intron	N/A	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.191+23046C>T		intron	N/A	ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22165 AN: 151988 Hom.: 1628 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.146 AC: 22206 AN: 152106 Hom.: 1637 Cov.: 32 AF XY: 0.146 AC XY: 10820 AN XY: 74332

African (AFR) AF: 0.128 AC: 5291 AN: 41474

American (AMR) AF: 0.156 AC: 2379 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3472

East Asian (EAS) AF: 0.0971 AC: 503 AN: 5180

South Asian (SAS) AF: 0.149 AC: 719 AN: 4810

European-Finnish (FIN) AF: 0.111 AC: 1168 AN: 10570

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11197 AN: 67998

Other (OTH) AF: 0.151 AC: 318 AN: 2108

Alfa AF: 0.150 Hom.: 2597

Bravo AF: 0.146

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.56
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: rs7082195; hg19: chr10-112427449;