12-130717490-C-T

Variant names:

• chr12-130717490-C-T
• rs10848190
• ENST00000691977.1:c.-262+50589G>A

Variant summary

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

The ENST00000691977.1(RIMBP2):​c.-262+50589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,100 control chromosomes in the GnomAD database, including 9,410 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 0.35 (9410 hom., cov: 34)
• Consequence: RIMBP2 ENST00000691977.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 3 publications found

Genes affected

RIMBP2 (HGNC:30339): (RIMS binding protein 2) Predicted to be involved in neuromuscular synaptic transmission. Predicted to be located in plasma membrane and synapse. Predicted to be active in presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000691977.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP2	ENST00000691977.1		c.-262+50589G>A		intron	N/A	ENSP00000510638.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52826 AN: 151982 Hom.: 9398 Cov.: 34

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.348 AC: 52869 AN: 152100 Hom.: 9410 Cov.: 34 AF XY: 0.348 AC XY: 25902 AN XY: 74366

African (AFR) AF: 0.285 AC: 11831 AN: 41500

American (AMR) AF: 0.328 AC: 5023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2038 AN: 5164

South Asian (SAS) AF: 0.358 AC: 1728 AN: 4826

European-Finnish (FIN) AF: 0.382 AC: 4034 AN: 10570

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25465 AN: 67958

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.379 Hom.: 5217

Bravo AF: 0.341

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		-0.034

Splicing

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

Other links and lift over

dbSNP: rs10848190; hg19: chr12-131202035;