rs200277475

Variant names:

• chr1-110340204-C-A
• rs200277475
• NM_022768.5:c.799C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-110340204-C-A
• chr1-110340204-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022768.5(RBM15):​c.799C>A​(p.Pro267Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P267S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM15 NM_022768.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061179966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM15	NM_022768.5	MANE Select	c.799C>A	p.Pro267Thr	missense	Exon 1 of 3	NP_073605.4
	RBM15	NM_001201545.2		c.799C>A	p.Pro267Thr	missense	Exon 1 of 2	NP_001188474.1	Q96T37-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM15	ENST00000369784.9	TSL:1 MANE Select	c.799C>A	p.Pro267Thr	missense	Exon 1 of 3	ENSP00000358799.3	Q96T37-1
	RBM15	ENST00000618772.4	TSL:1	c.799C>A	p.Pro267Thr	missense	Exon 1 of 3	ENSP00000483133.1	Q96T37-1
	RBM15	ENST00000487146.8	TSL:1	c.799C>A	p.Pro267Thr	missense	Exon 1 of 2	ENSP00000473552.3	Q96T37-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251190 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.80
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.074
Sift	Benign	0.30	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.30		Loss of sheet (P = 0.0126)
MVP		0.12
MPC		0.80
ClinPred		0.024	T
GERP RS		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.035
gMVP		0.59
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200277475; hg19: chr1-110882826;