rs75858380

Variant names:

• chr10-110821763-C-T
• rs75858380
• NM_001134363.3:c.3144C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001134363.3(RBM20):​c.3144C>T​(p.Ser1048Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,551,772 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (72 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 1.85
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 10-110821763-C-T is Benign according to our data. Variant chr10-110821763-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 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.3144C>T	p.Ser1048Ser	synonymous	Exon 11 of 14	NP_001127835.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.3144C>T	p.Ser1048Ser	synonymous	Exon 11 of 14	ENSP00000358532.3
	RBM20	ENST00000961386.1		c.3174C>T	p.Ser1058Ser	synonymous	Exon 11 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.3144C>T	p.Ser1048Ser	synonymous	Exon 11 of 14	ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2216 AN: 152198 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00327 AC: 513 AN: 156784 AF XY: 0.00241

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000494

Gnomad OTH exome AF: 0.000907

GnomAD4 exome AF: 0.00159 AC: 2227 AN: 1399456 Hom.: 72 Cov.: 33 AF XY: 0.00133 AC XY: 921 AN XY: 690240

African (AFR) AF: 0.0582 AC: 1839 AN: 31598

American (AMR) AF: 0.00316 AC: 113 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.000189 AC: 15 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49294

Middle Eastern (MID) AF: 0.00193 AC: 11 AN: 5698

European-Non Finnish (NFE) AF: 0.0000334 AC: 36 AN: 1078984

Other (OTH) AF: 0.00367 AC: 213 AN: 58022

GnomAD4 genome AF: 0.0146 AC: 2222 AN: 152316 Hom.: 56 Cov.: 32 AF XY: 0.0144 AC XY: 1069 AN XY: 74494

African (AFR) AF: 0.0509 AC: 2114 AN: 41568

American (AMR) AF: 0.00516 AC: 79 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2106

Alfa AF: 0.00642 Hom.: 8

Bravo AF: 0.0165

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	4	Dilated cardiomyopathy 1DD (4)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.5
DANN	Benign	0.81
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs75858380; hg19: chr10-112581521;