14-22900085-C-G

Position:

• chr14-22900085-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077351.2(RBM23):​c.*1645G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,824 control chromosomes in the GnomAD database, including 8,902 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 0.32 (8900 hom., cov: 30)
  • Exomes 𝑓: 0.32 (2 hom.)
• Consequence: RBM23 NM_001077351.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM23	NM_001077351.2	c.*1645G>C		3_prime_UTR_variant	14/14	ENST00000359890.8	NP_001070819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM23	ENST00000359890.8	c.*1645G>C		3_prime_UTR_variant	14/14	1	NM_001077351.2	ENSP00000352956	P2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48932 AN: 151684 Hom.: 8885 Cov.: 30

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.318 AC: 7 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 NFE exome AF: 0.318

GnomAD4 genome AF: 0.323 AC: 48985 AN: 151802 Hom.: 8900 Cov.: 30 AF XY: 0.323 AC XY: 23959 AN XY: 74202

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.289

Alfa AF: 0.153 Hom.: 281

Bravo AF: 0.326

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.74

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: rs3811187; hg19: chr14-23369294;