rs1832745

Positions:

• chr10-110813115-T-C
• chr10-110813115-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001134363.3(RBM20):​c.2550+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,116 control chromosomes in the GnomAD database, including 16,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (16526 hom., cov: 32)
• Consequence: RBM20 NM_001134363.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 10-110813115-T-C is Benign according to our data. Variant chr10-110813115-T-C is described in ClinVar as [Benign]. Clinvar id is 671184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.2550+168T>C		intron_variant		ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.2385+168T>C		intron_variant			XP_016871592.1
RBM20	XM_017016104.3	c.2166+168T>C		intron_variant			XP_016871593.1
RBM20	XM_047425116.1	c.2166+168T>C		intron_variant			XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.2550+168T>C		intron_variant		1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68797 AN: 151998 Hom.: 16522 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68832 AN: 152116 Hom.: 16526 Cov.: 32 AF XY: 0.458 AC XY: 34063 AN XY: 74344

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.457

Alfa AF: 0.509 Hom.: 19290

Bravo AF: 0.443

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.4
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1832745; hg19: chr10-112572873;