rs10848167

chr12-130639078-C-G

Variant summary

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

The NM_001393629.1(RIMBP2):c.-351-10622G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,990 control chromosomes in the GnomAD database, including 32,637 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 0.65 (32637 hom., cov: 32)
• Consequence: RIMBP2 NM_001393629.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMBP2	NM_001393629.1	c.-351-10622G>C		intron_variant		ENST00000690449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMBP2	ENST00000690449.1	c.-351-10622G>C		intron_variant			NM_001393629.1	P5

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99158 AN: 151872 Hom.: 32611 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.653 AC: 99231 AN: 151990 Hom.: 32637 Cov.: 32 AF XY: 0.661 AC XY: 49142 AN XY: 74302

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.678

Alfa AF: 0.650 Hom.: 4000

Bravo AF: 0.644

Asia WGS AF: 0.661 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10848167; hg19: chr12-131123623;