12-56535560-C-T

Variant names:

• chr12-56535560-C-T
• rs7314300
• NM_002898.4:c.66+13471C>T

Variant summary

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

The NM_002898.4(RBMS2):​c.66+13471C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 150,878 control chromosomes in the GnomAD database, including 14,764 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 0.42 (14764 hom., cov: 29)
• Consequence: RBMS2 NM_002898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002898.4. 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
	RBMS2	NM_002898.4	MANE Select	c.66+13471C>T		intron	N/A	NP_002889.1	Q15434
	RBMS2	NM_001414460.1		c.66+13471C>T		intron	N/A	NP_001401389.1
	RBMS2	NM_001414461.1		c.66+13471C>T		intron	N/A	NP_001401390.1	Q15434

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS2	ENST00000262031.10	TSL:1 MANE Select	c.66+13471C>T		intron	N/A	ENSP00000262031.5	Q15434
	RBMS2	ENST00000552916.5	TSL:1	n.66+13471C>T		intron	N/A	ENSP00000450127.1	F8VQS9
	RBMS2	ENST00000855893.1		c.66+13471C>T		intron	N/A	ENSP00000525952.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62788 AN: 150768 Hom.: 14759 Cov.: 29

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.416 AC: 62804 AN: 150878 Hom.: 14764 Cov.: 29 AF XY: 0.413 AC XY: 30384 AN XY: 73540

African (AFR) AF: 0.190 AC: 7835 AN: 41156

American (AMR) AF: 0.523 AC: 7878 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1967 AN: 3458

East Asian (EAS) AF: 0.599 AC: 3058 AN: 5108

South Asian (SAS) AF: 0.314 AC: 1509 AN: 4804

European-Finnish (FIN) AF: 0.470 AC: 4782 AN: 10178

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.506 AC: 34303 AN: 67816

Other (OTH) AF: 0.470 AC: 988 AN: 2102

Alfa AF: 0.489 Hom.: 23995

Bravo AF: 0.422

Asia WGS AF: 0.402 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		0.022
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: rs7314300; hg19: chr12-56929344;