12-130609800-T-C

Variant names:

• chr12-130609800-T-C
• rs4759499
• NM_001393629.1:c.-217+18522A>G

Variant summary

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

The NM_001393629.1(RIMBP2):​c.-217+18522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,072 control chromosomes in the GnomAD database, including 57,851 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 0.87 (57851 hom., cov: 30)
• Consequence: RIMBP2 NM_001393629.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP2	NM_001393629.1	c.-217+18522A>G		intron_variant	Intron 2 of 22	ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1	c.-217+18522A>G		intron_variant	Intron 2 of 22		NM_001393629.1	ENSP00000509157.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132464 AN: 151954 Hom.: 57801 Cov.: 30

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.872 AC: 132574 AN: 152072 Hom.: 57851 Cov.: 30 AF XY: 0.873 AC XY: 64863 AN XY: 74314

African (AFR) AF: 0.859 AC: 35654 AN: 41496

American (AMR) AF: 0.823 AC: 12581 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3219 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4361 AN: 5122

South Asian (SAS) AF: 0.907 AC: 4357 AN: 4806

European-Finnish (FIN) AF: 0.895 AC: 9463 AN: 10578

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60027 AN: 67998

Other (OTH) AF: 0.860 AC: 1815 AN: 2110

Alfa AF: 0.876 Hom.: 111007

Bravo AF: 0.864

Asia WGS AF: 0.895 AC: 3114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.93
DANN	Benign	0.70
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4759499; hg19: chr12-131094345;