12-130717490-C-T

Position:

• chr12-130717490-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMBP2	ENST00000691977.1	c.-262+50589G>A		intron_variant				P5

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.346

Alfa AF: 0.377 Hom.: 4505

Bravo AF: 0.341

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10848190; hg19: chr12-131202035;