12-130437119-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393629.1(RIMBP2):c.1829C>G(p.Pro610Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,583,406 control chromosomes in the GnomAD database, including 9 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 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (9 hom.)
• Consequence: RIMBP2 NM_001393629.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077821612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMBP2	NM_001393629.1	c.1829C>G	p.Pro610Arg	missense_variant	13/23	ENST00000690449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMBP2	ENST00000690449.1	c.1829C>G	p.Pro610Arg	missense_variant	13/23		NM_001393629.1	P5

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151386 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00704

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000526 AC: 115 AN: 218470 Hom.: 0 AF XY: 0.000475 AC XY: 56 AN XY: 117796

Gnomad AFR exome AF: 0.0000686

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00628

Gnomad SAS exome AF: 0.000233

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.000379 AC: 543 AN: 1431902 Hom.: 9 Cov.: 33 AF XY: 0.000381 AC XY: 270 AN XY: 708382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.000231

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.000237

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151504 Hom.: 0 Cov.: 33 AF XY: 0.000284 AC XY: 21 AN XY: 74072

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00706

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000277 Hom.: 0

Bravo AF: 0.000223

ExAC AF: 0.000521 AC: 63

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	16
Dann	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.0078	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;.;.
Sift4G	Benign	0.19	T;.;.
Polyphen		1.0	D;.;.
Vest4		0.35
MVP		0.67
MPC		0.69
ClinPred		0.13	T
GERP RS		2.6
Varity_R		0.22
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292664; hg19: chr12-130921664;