chr20-35652818-A-G

Position:

• chr20-35652818-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_006047.6(RBM12):​c.2505T>C​(p.Pro835Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,602,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: RBM12 NM_006047.6 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.00700

Genes affected

RBM12 (HGNC:9898): (RNA binding motif protein 12) This gene encodes a protein that contains several RNA-binding motifs, potential transmembrane domains, and proline-rich regions. This gene and the gene for copine I overlap at map location 20q11.21. Alternative splicing in the 5' UTR results in four transcript variants. All variants encode the same protein. [provided by RefSeq, Nov 2010]

CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

ENSG00000272897 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 20-35652818-A-G is Benign according to our data. Variant chr20-35652818-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3049197.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.007 with no splicing effect.
• BS2: High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6	c.2505T>C	p.Pro835Pro	synonymous_variant	3/3	ENST00000374114.8	NP_006038.2
CPNE1	NM_152925.3	c.-1+11942T>C		intron_variant		ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12	ENST00000374114.8	c.2505T>C	p.Pro835Pro	synonymous_variant	3/3	1	NM_006047.6	ENSP00000363228.3
CPNE1	ENST00000397443.7	c.-1+11942T>C		intron_variant		5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.-1+11984T>C		intron_variant		1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*32+2384T>C		intron_variant		2		ENSP00000443983.2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000935 AC: 22 AN: 235388 Hom.: 0 AF XY: 0.000109 AC XY: 14 AN XY: 128324

Gnomad AFR exome AF: 0.0000665

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000276

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000764

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.0000490 AC: 71 AN: 1450380 Hom.: 0 Cov.: 31 AF XY: 0.0000485 AC XY: 35 AN XY: 720942

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.000208

Gnomad4 ASJ exome AF: 0.0000400

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000425

Gnomad4 OTH exome AF: 0.000100

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74302

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.000478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RBM12-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.71

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: rs376657170; hg19: chr20-34240740; COSMIC: COSV58293392; COSMIC: COSV58293392;