chr10-110812296-G-T

Variant names:

• chr10-110812296-G-T
• rs1446760969
• NM_001134363.3:c.1899G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001134363.3(RBM20):​c.1899G>T​(p.Pro633Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P633P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.1899G>T	p.Pro633Pro	synonymous_variant	Exon 9 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.1734G>T	p.Pro578Pro	synonymous_variant	Exon 9 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.1515G>T	p.Pro505Pro	synonymous_variant	Exon 9 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.1515G>T	p.Pro505Pro	synonymous_variant	Exon 9 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.1899G>T	p.Pro633Pro	synonymous_variant	Exon 9 of 14	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.1899G>T	p.Pro633Pro	synonymous_variant	Exon 9 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394236 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 686780

African (AFR) AF: 0.00 AC: 0 AN: 31494

American (AMR) AF: 0.00 AC: 0 AN: 35538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25094

East Asian (EAS) AF: 0.00 AC: 0 AN: 35594

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075766

Other (OTH) AF: 0.00 AC: 0 AN: 57828

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.40
PhyloP100		-3.7

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: rs1446760969; hg19: chr10-112572054;