14-22905653-C-T

Position:

• chr14-22905653-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001077351.2(RBM23):​c.408G>A​(p.Arg136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,600,434 control chromosomes in the GnomAD database, including 267,948 homozygotes. 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: 𝑓 0.46 (19841 hom., cov: 32)
  • Exomes 𝑓: 0.58 (248107 hom.)
• Consequence: RBM23 NM_001077351.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

Genes affected

RBM23 (HGNC:20155): (RNA binding motif protein 23) This gene encodes a member of the U2AF-like family of RNA binding proteins. This protein interacts with some steroid nuclear receptors, localizes to the promoter of a steroid- responsive gene, and increases transcription of steroid-responsive transcriptional reporters in a hormone-dependent manner. It is also implicated in the steroid receptor-dependent regulation of alternative splicing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.943 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM23	NM_001077351.2	c.408G>A	p.Arg136=	synonymous_variant	6/14	ENST00000359890.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM23	ENST00000359890.8	c.408G>A	p.Arg136=	synonymous_variant	6/14	1	NM_001077351.2	P2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70180 AN: 151952 Hom.: 19835 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.508

GnomAD3 exomes AF: 0.589 AC: 146819 AN: 249212 Hom.: 45800 AF XY: 0.598 AC XY: 80819 AN XY: 135230

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.651

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.790

Gnomad SAS exome AF: 0.712

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.578 AC: 836547 AN: 1448364 Hom.: 248107 Cov.: 33 AF XY: 0.583 AC XY: 420424 AN XY: 721302

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.462 AC: 70183 AN: 152070 Hom.: 19841 Cov.: 32 AF XY: 0.469 AC XY: 34820 AN XY: 74310

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.506

Alfa AF: 0.554 Hom.: 40270

Bravo AF: 0.447

Asia WGS AF: 0.699 AC: 2429 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295682; hg19: chr14-23374862; COSMIC: COSV57128534; COSMIC: COSV57128534;