chr10-110644453-G-T

Variant names:

• chr10-110644453-G-T
• rs1467185349
• NM_001134363.3:c.-2G>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.-2G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,334,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: RBM20 NM_001134363.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0590
• 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=-0.58).

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.-2G>T		5_prime_UTR	Exon 1 of 14	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.-2G>T		5_prime_UTR	Exon 1 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.-2G>T		5_prime_UTR	Exon 1 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.-2G>T		5_prime_UTR	Exon 1 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1334588 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 656946

African (AFR) AF: 0.00 AC: 0 AN: 26880

American (AMR) AF: 0.00 AC: 0 AN: 28584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23250

East Asian (EAS) AF: 0.00 AC: 0 AN: 30306

South Asian (SAS) AF: 0.00 AC: 0 AN: 72916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1054646

Other (OTH) AF: 0.0000181 AC: 1 AN: 55262

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		-0.059
PromoterAI		-0.0044	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: rs1467185349; hg19: chr10-112404211;