12-130618798-C-T

Position:

• chr12-130618798-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP2	NM_001393629.1	c.-217+9524G>A		intron_variant		ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1	c.-217+9524G>A		intron_variant			NM_001393629.1	ENSP00000509157.1

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

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.491

Alfa AF: 0.458 Hom.: 21402

Bravo AF: 0.506

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.099
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1487602; hg19: chr12-131103343;