rs12572941

Variant names:

• chr10-110810372-G-C
• rs12572941
• NM_001134363.3:c.1801-11G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-110810372-G-C
• chr10-110810372-G-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001134363.3(RBM20):​c.1801-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,549,418 control chromosomes in the GnomAD database, including 876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (82 hom., cov: 32)
  • Exomes 𝑓: 0.027 (794 hom.)
• Consequence: RBM20 NM_001134363.3 intron
• Scores: Splicing: ADA: 0.00003465
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.296
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-110810372-G-C is Benign according to our data. Variant chr10-110810372-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0925 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.1801-11G>C		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.1801-11G>C		intron	N/A	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.1831-11G>C		intron	N/A	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.1801-11G>C		intron	N/A	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4033 AN: 152150 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.0350 AC: 5478 AN: 156494 AF XY: 0.0388

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0225

Gnomad EAS exome AF: 0.0288

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0232

Gnomad OTH exome AF: 0.0314

GnomAD4 exome AF: 0.0270 AC: 37697 AN: 1397150 Hom.: 794 Cov.: 30 AF XY: 0.0291 AC XY: 20034 AN XY: 689216

African (AFR) AF: 0.0256 AC: 808 AN: 31558

American (AMR) AF: 0.0182 AC: 649 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 569 AN: 25162

East Asian (EAS) AF: 0.0246 AC: 879 AN: 35708

South Asian (SAS) AF: 0.0941 AC: 7445 AN: 79096

European-Finnish (FIN) AF: 0.0379 AC: 1867 AN: 49224

Middle Eastern (MID) AF: 0.0450 AC: 256 AN: 5694

European-Non Finnish (NFE) AF: 0.0217 AC: 23427 AN: 1077106

Other (OTH) AF: 0.0310 AC: 1797 AN: 57912

GnomAD4 genome AF: 0.0265 AC: 4042 AN: 152268 Hom.: 82 Cov.: 32 AF XY: 0.0282 AC XY: 2103 AN XY: 74460

African (AFR) AF: 0.0264 AC: 1096 AN: 41534

American (AMR) AF: 0.0214 AC: 327 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5186

South Asian (SAS) AF: 0.0998 AC: 481 AN: 4818

European-Finnish (FIN) AF: 0.0341 AC: 362 AN: 10610

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0215 AC: 1461 AN: 68030

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0151 Hom.: 9

Bravo AF: 0.0243

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Dilated cardiomyopathy 1DD (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.77
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000035
dbscSNV1_RF	Benign	0.024
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: rs12572941; hg19: chr10-112570130;