NM_001393629.1:c.-217+9524G>A

Variant names:

• chr12-130618798-C-T
• rs1487602
• NM_001393629.1:c.-217+9524G>A

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+9524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,004 control chromosomes in the GnomAD database, including 19,284 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 0.50 (19284 hom., cov: 32)
• Consequence: RIMBP2 NM_001393629.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393629.1. 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
	RIMBP2	NM_001393629.1	MANE Select	c.-217+9524G>A		intron	N/A	NP_001380558.1
	RIMBP2	NM_001393614.1		c.-217+9524G>A		intron	N/A	NP_001380543.1
	RIMBP2	NM_001393615.1		c.-127+9524G>A		intron	N/A	NP_001380544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP2	ENST00000690449.1	MANE Select	c.-217+9524G>A		intron	N/A	ENSP00000509157.1
	RIMBP2	ENST00000643940.1		c.-127+9524G>A		intron	N/A	ENSP00000495590.1
	RIMBP2	ENST00000691977.1		c.-127+9524G>A		intron	N/A	ENSP00000510638.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75899 AN: 151886 Hom.: 19251 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.500 AC: 75980 AN: 152004 Hom.: 19284 Cov.: 32 AF XY: 0.503 AC XY: 37399 AN XY: 74292

African (AFR) AF: 0.570 AC: 23617 AN: 41460

American (AMR) AF: 0.564 AC: 8619 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2461 AN: 5174

South Asian (SAS) AF: 0.516 AC: 2482 AN: 4810

European-Finnish (FIN) AF: 0.477 AC: 5029 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30861 AN: 67962

Other (OTH) AF: 0.491 AC: 1037 AN: 2112

Alfa AF: 0.464 Hom.: 27996

Bravo AF: 0.506

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.099
DANN	Benign	0.71
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1487602; hg19: chr12-131103343;