rs397516614

Variant names:

• chr10-110823535-T-C
• rs397516614
• NM_001134363.3:c.3372T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001134363.3(RBM20):​c.3372T>C​(p.Thr1124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,542,908 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RBM20 NM_001134363.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.79
• 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), 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-110823535-T-C is Benign according to our data. Variant chr10-110823535-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 44008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.79 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 39 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.3372T>C	p.Thr1124Thr	synonymous	Exon 12 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.3372T>C	p.Thr1124Thr	synonymous	Exon 12 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.3402T>C	p.Thr1134Thr	synonymous	Exon 12 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.3372T>C	p.Thr1124Thr	synonymous	Exon 12 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147310 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156524 AF XY: 0.0000241

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000330

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000279 AC: 39 AN: 1395598 Hom.: 0 Cov.: 35 AF XY: 0.0000247 AC XY: 17 AN XY: 688248

African (AFR) AF: 0.00 AC: 0 AN: 31224

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35560

South Asian (SAS) AF: 0.00 AC: 0 AN: 79188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.0000353 AC: 38 AN: 1076666

Other (OTH) AF: 0.0000173 AC: 1 AN: 57698

GnomAD4 genome AF: 0.00000679 AC: 1 AN: 147310 Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 1 AN XY: 71620

African (AFR) AF: 0.00 AC: 0 AN: 39322

American (AMR) AF: 0.00 AC: 0 AN: 14342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67506

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.0000282 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.47
DANN	Benign	0.68
PhyloP100		-4.8

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: rs397516614; hg19: chr10-112583293;