rs7070640

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134363.3(RBM20):​c.3452-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM20 NM_001134363.3 intron
• Scores: Splicing: ADA: 0.0004307
• Clinical Significance: Not reported in ClinVar
• 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), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.3452-9C>A		intron_variant	Intron 12 of 13	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.3287-9C>A		intron_variant	Intron 12 of 13		XP_016871592.1
RBM20	XM_017016104.3	c.3068-9C>A		intron_variant	Intron 12 of 13		XP_016871593.1
RBM20	XM_047425116.1	c.3068-9C>A		intron_variant	Intron 12 of 13		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.3452-9C>A		intron_variant	Intron 12 of 13	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.3452-9C>A		intron_variant	Intron 12 of 13			ENSP00000520684.1
RBM20	ENST00000471172.1	n.28-9C>A		intron_variant	Intron 1 of 1	5
RBM20	ENST00000480343.2	n.85-9C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2779

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.040
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: rs7070640; hg19: chr10-112590810;