20-35652914-C-T

Position:

• chr20-35652914-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006047.6(RBM12):​c.2409G>A​(p.Pro803Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,613,718 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (115 hom.)
• Consequence: RBM12 NM_006047.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.486

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-35652914-C-T is Benign according to our data. Variant chr20-35652914-C-T is described in ClinVar as [Benign]. Clinvar id is 769998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.486 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6	c.2409G>A	p.Pro803Pro	synonymous_variant	3/3	ENST00000374114.8	NP_006038.2
CPNE1	NM_152925.3	c.-1+11846G>A		intron_variant		ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12	ENST00000374114.8	c.2409G>A	p.Pro803Pro	synonymous_variant	3/3	1	NM_006047.6	ENSP00000363228.3
CPNE1	ENST00000397443.7	c.-1+11846G>A		intron_variant		5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.-1+11888G>A		intron_variant		1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*32+2288G>A		intron_variant		2		ENSP00000443983.2

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152204 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0102 AC: 2492 AN: 245422 Hom.: 101 AF XY: 0.00748 AC XY: 1002 AN XY: 133892

Gnomad AFR exome AF: 0.000332

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000549

Gnomad OTH exome AF: 0.00678

GnomAD4 exome AF: 0.00203 AC: 2964 AN: 1461396 Hom.: 115 Cov.: 32 AF XY: 0.00166 AC XY: 1205 AN XY: 726994

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0631

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152322 Hom.: 14 Cov.: 32 AF XY: 0.00305 AC XY: 227 AN XY: 74486

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00629

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs149878650; hg19: chr20-34240836;