rs76048624

Variant names:

• chr10-110797582-C-T
• rs76048624
• NM_001134363.3:c.1602C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-110797582-C-T
• chr10-110797582-C-A
• chr10-110797582-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_001134363.3(RBM20):​c.1602C>T​(p.Asp534Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,551,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:9
• Conservation: PhyloP100: 0.154
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 10-110797582-C-T is Benign according to our data. Variant chr10-110797582-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 198123.
• BP7: Synonymous conserved (PhyloP=0.154 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000959 (146/152208) while in subpopulation AFR AF = 0.00335 (139/41494). AF 95% confidence interval is 0.0029. There are 0 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 146 AD gene.

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.1602C>T	p.Asp534Asp	synonymous	Exon 6 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.1602C>T	p.Asp534Asp	synonymous	Exon 6 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.1632C>T	p.Asp544Asp	synonymous	Exon 6 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.1602C>T	p.Asp534Asp	synonymous	Exon 6 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.000960 AC: 146 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000172 AC: 27 AN: 157270 AF XY: 0.000168

Gnomad AFR exome AF: 0.00186

Gnomad AMR exome AF: 0.0000810

Gnomad ASJ exome AF: 0.000353

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000983

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000900 AC: 126 AN: 1399436 Hom.: 0 Cov.: 30 AF XY: 0.0000855 AC XY: 59 AN XY: 690230

African (AFR) AF: 0.00250 AC: 79 AN: 31596

American (AMR) AF: 0.0000840 AC: 3 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25182

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

South Asian (SAS) AF: 0.0000505 AC: 4 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49318

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5688

European-Non Finnish (NFE) AF: 0.0000185 AC: 20 AN: 1078952

Other (OTH) AF: 0.000207 AC: 12 AN: 58028

GnomAD4 genome AF: 0.000959 AC: 146 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74398

African (AFR) AF: 0.00335 AC: 139 AN: 41494

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000409 Hom.: 0

Bravo AF: 0.000903

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	4	not specified (4)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated cardiomyopathy 1DD (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.1
DANN	Benign	0.56
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs76048624; hg19: chr10-112557340; COSMIC: COSV65705978;