10-110659431-A-G

Position:

• chr10-110659431-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+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

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 = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.191+14786A>G		intron_variant		ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+15991A>G		intron_variant			XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.191+14786A>G		intron_variant		1	NM_001134363.3	ENSP00000358532	P1

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

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.243

Alfa AF: 0.296 Hom.: 10115

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

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: rs10509923; hg19: chr10-112419189;