rs1572263

Positions:

• chr1-110343114-G-A
• chr1-110343114-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022768.5(RBM15):​c.2863+846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,044 control chromosomes in the GnomAD database, including 46,294 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 0.78 (46294 hom., cov: 32)
• Consequence: RBM15 NM_022768.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

RBM15 (HGNC:14959): (RNA binding motif protein 15) Members of the SPEN (Split-end) family of proteins, including RBM15, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM15	NM_022768.5	c.2863+846G>A		intron_variant		ENST00000369784.9	NP_073605.4
RBM15	NM_001201545.2	c.2863+846G>A		intron_variant			NP_001188474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM15	ENST00000369784.9	c.2863+846G>A		intron_variant		1	NM_022768.5	ENSP00000358799.3

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117969 AN: 151926 Hom.: 46242 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.777 AC: 118080 AN: 152044 Hom.: 46294 Cov.: 32 AF XY: 0.775 AC XY: 57598 AN XY: 74322

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.743

Alfa AF: 0.730 Hom.: 82803

Bravo AF: 0.788

Asia WGS AF: 0.757 AC: 2634 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1572263; hg19: chr1-110885736;