chr10-110644439-G-C

Variant names:

• chr10-110644439-G-C
• rs876657975
• NM_001134363.3:c.-16G>C

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.-16G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,454 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: 7.6e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.-16G>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+999G>C		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.-16G>C		5_prime_UTR_variant	Exon 1 of 14	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.-16G>C		5_prime_UTR_variant	Exon 1 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310454 Hom.: 0 Cov.: 30 AF XY: 0.00000155 AC XY: 1 AN XY: 643398

African (AFR) AF: 0.00 AC: 0 AN: 26224

American (AMR) AF: 0.00 AC: 0 AN: 24190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22056

East Asian (EAS) AF: 0.00 AC: 0 AN: 29614

South Asian (SAS) AF: 0.00 AC: 0 AN: 69120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3826

European-Non Finnish (NFE) AF: 9.58e-7 AC: 1 AN: 1044210

Other (OTH) AF: 0.00 AC: 0 AN: 54268

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		1.7
PromoterAI		0.090	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: rs876657975; hg19: chr10-112404197;