rs397516589

Variant names:

• chr10-110644449-C-A
• rs397516589
• NM_001134363.3:c.-6C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110644449-C-A
• chr10-110644449-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.-6C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,331,056 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RBM20 NM_001134363.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• 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), 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=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.-6C>A		5_prime_UTR_variant	Exon 1 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+1009C>A		intron_variant	Intron 1 of 13		XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.-6C>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.-6C>A		5_prime_UTR_variant	Exon 1 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1331056 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 655008

African (AFR) AF: 0.00 AC: 0 AN: 26780

American (AMR) AF: 0.00 AC: 0 AN: 27746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23030

East Asian (EAS) AF: 0.00 AC: 0 AN: 30286

South Asian (SAS) AF: 0.00 AC: 0 AN: 72136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3924

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1053634

Other (OTH) AF: 0.00 AC: 0 AN: 55158

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		-0.37
PromoterAI		0.060	Neutral

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: rs397516589; hg19: chr10-112404207;