12-56544599-T-G

Variant names:

• chr12-56544599-T-G
• rs2657888
• NM_002898.4:c.67-17818T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002898.4(RBMS2):​c.67-17818T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,754 control chromosomes in the GnomAD database, including 27,579 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 0.60 (27579 hom., cov: 30)
• Consequence: RBMS2 NM_002898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 22 publications found

Genes affected

RBMS2 (HGNC:9909): (RNA binding motif single stranded interacting protein 2) The protein encoded by this gene is a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. The RBMS proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. This protein was isolated by phenotypic complementation of cdc2 and cdc13 mutants of yeast and is thought to suppress cdc2 and cdc13 mutants through the induction of translation of cdc2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS2	NM_002898.4	c.67-17818T>G		intron_variant	Intron 1 of 13	ENST00000262031.10	NP_002889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS2	ENST00000262031.10	c.67-17818T>G		intron_variant	Intron 1 of 13	1	NM_002898.4	ENSP00000262031.5

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90391 AN: 151636 Hom.: 27575 Cov.: 30

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.596 AC: 90439 AN: 151754 Hom.: 27579 Cov.: 30 AF XY: 0.594 AC XY: 44026 AN XY: 74142

African (AFR) AF: 0.476 AC: 19672 AN: 41368

American (AMR) AF: 0.658 AC: 10012 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2396 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3679 AN: 5152

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4810

European-Finnish (FIN) AF: 0.615 AC: 6457 AN: 10506

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43853 AN: 67928

Other (OTH) AF: 0.632 AC: 1329 AN: 2102

Alfa AF: 0.630 Hom.: 71755

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2657888; hg19: chr12-56938383;