rs138436392

Variant names:

• chr10-110812275-C-T
• rs138436392
• NM_001134363.3:c.1881-3C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-110812275-C-T
• chr10-110812275-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001134363.3(RBM20):​c.1881-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000979 in 1,537,790 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (6 hom.)
• Consequence: RBM20 NM_001134363.3 splice_region, intron
• Scores: Splicing: ADA: 0.009770
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: 2.84
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-110812275-C-T is Benign according to our data. Variant chr10-110812275-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00521 (794/152308) while in subpopulation AFR AF = 0.0182 (755/41566). AF 95% confidence interval is 0.0171. There are 11 homozygotes in GnomAd4. There are 364 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 794 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.1881-3C>T		splice_region intron	N/A	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.1881-3C>T		splice_region intron	N/A	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.1911-3C>T		splice_region intron	N/A	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.1881-3C>T		splice_region intron	N/A	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 792 AN: 152190 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.000998 AC: 146 AN: 146224 AF XY: 0.000819

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000537

Gnomad OTH exome AF: 0.000478

GnomAD4 exome AF: 0.000514 AC: 712 AN: 1385482 Hom.: 6 Cov.: 32 AF XY: 0.000451 AC XY: 307 AN XY: 681360

African (AFR) AF: 0.0199 AC: 623 AN: 31370

American (AMR) AF: 0.000313 AC: 11 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24728

East Asian (EAS) AF: 0.00 AC: 0 AN: 35468

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46358

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5650

European-Non Finnish (NFE) AF: 0.0000252 AC: 27 AN: 1070898

Other (OTH) AF: 0.000818 AC: 47 AN: 57452

GnomAD4 genome AF: 0.00521 AC: 794 AN: 152308 Hom.: 11 Cov.: 32 AF XY: 0.00489 AC XY: 364 AN XY: 74464

African (AFR) AF: 0.0182 AC: 755 AN: 41566

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00275 Hom.: 1

Bravo AF: 0.00574

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	4	Dilated cardiomyopathy 1DD (4)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		2.8
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0098
dbscSNV1_RF	Benign	0.17
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: rs138436392; hg19: chr10-112572033;