rs35141404

Variant names:

• chr10-110644544-G-A
• rs35141404
• NM_001134363.3:c.90G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001134363.3(RBM20):​c.90G>A​(p.Arg30Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,526,416 control chromosomes in the GnomAD database, including 21,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3977 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17109 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: 0.140
• Publications: 11 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), G2P, Ambry Genetics
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 10-110644544-G-A is Benign according to our data. Variant chr10-110644544-G-A is described in ClinVar as Benign. ClinVar VariationId is 44029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	NM_001134363.3	MANE Select	c.90G>A	p.Arg30Arg	synonymous	Exon 1 of 14	NP_001127835.2	Q5T481

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.90G>A	p.Arg30Arg	synonymous	Exon 1 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.90G>A	p.Arg30Arg	synonymous	Exon 1 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.90G>A	p.Arg30Arg	synonymous	Exon 1 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30937 AN: 151750 Hom.: 3968 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0971

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.143 AC: 17277 AN: 120516 AF XY: 0.144

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.152 AC: 208355 AN: 1374558 Hom.: 17109 Cov.: 33 AF XY: 0.151 AC XY: 102151 AN XY: 677954

African (AFR) AF: 0.388 AC: 11334 AN: 29200

American (AMR) AF: 0.108 AC: 3672 AN: 34018

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2465 AN: 24470

East Asian (EAS) AF: 0.186 AC: 6320 AN: 33946

South Asian (SAS) AF: 0.146 AC: 11319 AN: 77508

European-Finnish (FIN) AF: 0.0959 AC: 4026 AN: 41960

Middle Eastern (MID) AF: 0.143 AC: 580 AN: 4058

European-Non Finnish (NFE) AF: 0.149 AC: 159942 AN: 1072404

Other (OTH) AF: 0.153 AC: 8697 AN: 56994

GnomAD4 genome AF: 0.204 AC: 30977 AN: 151858 Hom.: 3977 Cov.: 32 AF XY: 0.199 AC XY: 14787 AN XY: 74196

African (AFR) AF: 0.370 AC: 15309 AN: 41396

American (AMR) AF: 0.148 AC: 2262 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3468

East Asian (EAS) AF: 0.161 AC: 821 AN: 5108

South Asian (SAS) AF: 0.141 AC: 681 AN: 4822

European-Finnish (FIN) AF: 0.0971 AC: 1028 AN: 10592

Middle Eastern (MID) AF: 0.147 AC: 42 AN: 286

European-Non Finnish (NFE) AF: 0.147 AC: 9975 AN: 67890

Other (OTH) AF: 0.191 AC: 402 AN: 2106

Alfa AF: 0.157 Hom.: 541

Bravo AF: 0.215

Asia WGS AF: 0.186 AC: 647 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	10	not specified (10)
-	-	2	Dilated cardiomyopathy 1DD (2)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		0.14
PromoterAI		-0.0096	Neutral
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: rs35141404; hg19: chr10-112404302; COSMIC: COSV65702521; COSMIC: COSV65702521;