chr10-110644607-G-C

Variant names:

• chr10-110644607-G-C
• rs760605118
• NM_001134363.3:c.153G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001134363.3(RBM20):​c.153G>C​(p.Pro51Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. P51P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.

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.153G>C	p.Pro51Pro	synonymous	Exon 1 of 14	NP_001127835.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.153G>C	p.Pro51Pro	synonymous	Exon 1 of 14	ENSP00000358532.3
	RBM20	ENST00000718239.1		c.153G>C	p.Pro51Pro	synonymous	Exon 1 of 14	ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.0000481 AC: 7 AN: 145508 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000450

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00150 AC: 1411 AN: 939818 Hom.: 0 Cov.: 33 AF XY: 0.00140 AC XY: 660 AN XY: 472454

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00214 AC: 42 AN: 19636

American (AMR) AF: 0.000141 AC: 4 AN: 28438

Ashkenazi Jewish (ASJ) AF: 0.000916 AC: 16 AN: 17460

East Asian (EAS) AF: 0.000491 AC: 11 AN: 22400

South Asian (SAS) AF: 0.000391 AC: 27 AN: 69070

European-Finnish (FIN) AF: 0.0000737 AC: 2 AN: 27142

Middle Eastern (MID) AF: 0.00131 AC: 4 AN: 3050

European-Non Finnish (NFE) AF: 0.00175 AC: 1253 AN: 714464

Other (OTH) AF: 0.00136 AC: 52 AN: 38158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000481 AC: 7 AN: 145652 Hom.: 0 Cov.: 32 AF XY: 0.0000282 AC XY: 2 AN XY: 71046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000496 AC: 2 AN: 40324

American (AMR) AF: 0.00 AC: 0 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.000451 AC: 2 AN: 4434

South Asian (SAS) AF: 0.00 AC: 0 AN: 4092

European-Finnish (FIN) AF: 0.000216 AC: 2 AN: 9258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66178

Other (OTH) AF: 0.00 AC: 0 AN: 2060

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.7
DANN	Benign	0.87
PhyloP100		1.6
PromoterAI		-0.086	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs760605118; hg19: chr10-112404365;