chr14-22898976-C-A

Position:

• chr14-22898976-C-A

Variant summary

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

The NM_001077351.2(RBM23):​c.*2754G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,876 control chromosomes in the GnomAD database, including 8,669 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 (8666 hom., cov: 31)
  • Exomes 𝑓: 0.33 (3 hom.)
• Consequence: RBM23 NM_001077351.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM23	NM_001077351.2	c.*2754G>T		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.*2754G>T		3_prime_UTR_variant	14/14	1	NM_001077351.2	ENSP00000352956	P2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48367 AN: 151706 Hom.: 8654 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.327 AC: 17 AN: 52 Hom.: 3 Cov.: 0 AF XY: 0.306 AC XY: 11 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.319 AC: 48412 AN: 151824 Hom.: 8666 Cov.: 31 AF XY: 0.319 AC XY: 23689 AN XY: 74192

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.285

Alfa AF: 0.236 Hom.: 2366

Bravo AF: 0.322

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.60

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: rs1570342; hg19: chr14-23368185;