14-22905653-C-T

Variant names:

• chr14-22905653-C-T
• rs2295682
• NM_001077351.2:c.408G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001077351.2(RBM23):​c.408G>A​(p.Arg136Arg) 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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBM23	NM_001077351.2	c.408G>A	p.Arg136Arg	synonymous_variant	Exon 6 of 14	ENST00000359890.8	NP_001070819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM23	ENST00000359890.8	c.408G>A	p.Arg136Arg	synonymous_variant	Exon 6 of 14	1	NM_001077351.2	ENSP00000352956.3

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

GnomAD2 exomes AF: 0.589 AC: 146819 AN: 249212 AF XY: 0.598

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 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

African (AFR) AF: 0.103 AC: 3441 AN: 33392

American (AMR) AF: 0.643 AC: 28703 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 14331 AN: 26058

East Asian (EAS) AF: 0.793 AC: 31428 AN: 39614

South Asian (SAS) AF: 0.707 AC: 60746 AN: 85932

European-Finnish (FIN) AF: 0.567 AC: 30254 AN: 53396

Middle Eastern (MID) AF: 0.584 AC: 3352 AN: 5736

European-Non Finnish (NFE) AF: 0.573 AC: 630077 AN: 1099658

Other (OTH) AF: 0.571 AC: 34215 AN: 59914

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

African (AFR) AF: 0.121 AC: 5017 AN: 41474

American (AMR) AF: 0.551 AC: 8419 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4102 AN: 5182

South Asian (SAS) AF: 0.699 AC: 3372 AN: 4822

European-Finnish (FIN) AF: 0.568 AC: 6002 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39437 AN: 67956

Other (OTH) AF: 0.506 AC: 1069 AN: 2112

Alfa AF: 0.545 Hom.: 47745

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
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs2295682; hg19: chr14-23374862; COSMIC: COSV57128534; COSMIC: COSV57128534;