rs1464108

Positions:

• chr12-130537465-A-C
• chr12-130537465-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393629.1(RIMBP2):​c.-216-19548T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,114 control chromosomes in the GnomAD database, including 35,144 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 0.67 (35144 hom., cov: 32)
• Consequence: RIMBP2 NM_001393629.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP2	NM_001393629.1	c.-216-19548T>G		intron_variant		ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1	c.-216-19548T>G		intron_variant			NM_001393629.1	ENSP00000509157	P5

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102497 AN: 151996 Hom.: 35111 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.674 AC: 102583 AN: 152114 Hom.: 35144 Cov.: 32 AF XY: 0.681 AC XY: 50597 AN XY: 74336

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.666

Alfa AF: 0.678 Hom.: 64142

Bravo AF: 0.670

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.1
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1464108; hg19: chr12-131022010;