chr12-130437119-G-C

Variant names:

• chr12-130437119-G-C
• rs2292664
• NM_001393629.1:c.1829C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Publications: 6 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077821612).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.1829C>G	p.Pro610Arg	missense	Exon 13 of 23	NP_001380558.1
	RIMBP2	NM_001393614.1		c.1829C>G	p.Pro610Arg	missense	Exon 13 of 23	NP_001380543.1
	RIMBP2	NM_001393615.1		c.1829C>G	p.Pro610Arg	missense	Exon 12 of 21	NP_001380544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP2	ENST00000690449.1	MANE Select	c.1829C>G	p.Pro610Arg	missense	Exon 13 of 23	ENSP00000509157.1
	RIMBP2	ENST00000261655.8	TSL:1	c.1778C>G	p.Pro593Arg	missense	Exon 10 of 19	ENSP00000261655.4
	RIMBP2	ENST00000643940.1		c.1829C>G	p.Pro610Arg	missense	Exon 12 of 22	ENSP00000495590.1

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

GnomAD2 exomes AF: 0.000526 AC: 115 AN: 218470 AF XY: 0.000475

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 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

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.00 AC: 0 AN: 41752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24328

East Asian (EAS) AF: 0.0131 AC: 509 AN: 38958

South Asian (SAS) AF: 0.000231 AC: 19 AN: 82110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095514

Other (OTH) AF: 0.000237 AC: 14 AN: 58996

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

African (AFR) AF: 0.00 AC: 0 AN: 41278

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00706 AC: 36 AN: 5100

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67776

Other (OTH) AF: 0.00 AC: 0 AN: 2096

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 v4.9

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
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.3
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
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs2292664; hg19: chr12-130921664;