chr10-110659431-A-G

Variant names:

• chr10-110659431-A-G
• rs10509923
• NM_001134363.3:c.191+14786A>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+14786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,166 control chromosomes in the GnomAD database, including 4,662 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 0.22 (4662 hom., cov: 31)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.191+14786A>G		intron_variant	Intron 1 of 13	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+15991A>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+14786A>G		intron_variant	Intron 1 of 13	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.191+14786A>G		intron_variant	Intron 1 of 13			ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33643 AN: 152048 Hom.: 4666 Cov.: 31

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.221 AC: 33638 AN: 152166 Hom.: 4662 Cov.: 31 AF XY: 0.219 AC XY: 16287 AN XY: 74404

African (AFR) AF: 0.0729 AC: 3031 AN: 41560

American (AMR) AF: 0.212 AC: 3235 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5182

South Asian (SAS) AF: 0.162 AC: 782 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3506 AN: 10572

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21218 AN: 67974

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.275 Hom.: 16663

Bravo AF: 0.207

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.79
PhyloP100		-0.15
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: rs10509923; hg19: chr10-112419189;