rs7070640

Variant names:

• chr10-110831052-C-G
• rs7070640
• NM_001134363.3:c.3452-9C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110831052-C-G
• chr10-110831052-C-A
• chr10-110831052-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134363.3(RBM20):​c.3452-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,548,570 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (194 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (218 hom.)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.230
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-110831052-C-G is Benign according to our data. Variant chr10-110831052-C-G is described in ClinVar as Benign. ClinVar VariationId is 3894996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 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.3452-9C>G		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.3452-9C>G		intron	N/A	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.3482-9C>G		intron	N/A	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.3452-9C>G		intron	N/A	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4344 AN: 152134 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00292 AC: 4073 AN: 1396318 Hom.: 218 Cov.: 30 AF XY: 0.00248 AC XY: 1710 AN XY: 688160

African (AFR) AF: 0.107 AC: 3372 AN: 31534

American (AMR) AF: 0.00539 AC: 192 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25124

East Asian (EAS) AF: 0.00 AC: 0 AN: 35646

South Asian (SAS) AF: 0.000304 AC: 24 AN: 79064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49248

Middle Eastern (MID) AF: 0.00317 AC: 18 AN: 5684

European-Non Finnish (NFE) AF: 0.0000771 AC: 83 AN: 1076584

Other (OTH) AF: 0.00664 AC: 384 AN: 57814

GnomAD4 genome AF: 0.0286 AC: 4360 AN: 152252 Hom.: 194 Cov.: 32 AF XY: 0.0275 AC XY: 2049 AN XY: 74452

African (AFR) AF: 0.0998 AC: 4142 AN: 41518

American (AMR) AF: 0.00987 AC: 151 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68018

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.117 Hom.: 2779

Bravo AF: 0.0328

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7070640; hg19: chr10-112590810;