20-35652818-AGGGCCG-A

Position:

• chr20-35652818-AGGGCCG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006047.6(RBM12):​c.2499_2504del​(p.Gly836_Pro837del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,602,592 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: RBM12 NM_006047.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.07

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-35652818-AGGGCCG-A is Benign according to our data. Variant chr20-35652818-AGGGCCG-A is described in ClinVar as [Benign]. Clinvar id is 3050136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM12	NM_006047.6	c.2499_2504del	p.Gly836_Pro837del	inframe_deletion	3/3	ENST00000374114.8
CPNE1	NM_152925.3	c.-1+11936_-1+11941del		intron_variant		ENST00000397443.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM12	ENST00000374114.8	c.2499_2504del	p.Gly836_Pro837del	inframe_deletion	3/3	1	NM_006047.6	P1
CPNE1	ENST00000397443.7	c.-1+11936_-1+11941del		intron_variant		5	NM_152925.3	P1

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 229 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000883

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00155 AC: 366 AN: 235388 Hom.: 2 AF XY: 0.00146 AC XY: 187 AN XY: 128324

Gnomad AFR exome AF: 0.000598

Gnomad AMR exome AF: 0.000514

Gnomad ASJ exome AF: 0.00402

Gnomad EAS exome AF: 0.000332

Gnomad SAS exome AF: 0.000239

Gnomad FIN exome AF: 0.00952

Gnomad NFE exome AF: 0.000793

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00105 AC: 1525 AN: 1450388 Hom.: 3 AF XY: 0.000997 AC XY: 719 AN XY: 720950

Gnomad4 AFR exome AF: 0.000575

Gnomad4 AMR exome AF: 0.000509

Gnomad4 ASJ exome AF: 0.00436

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.000212

Gnomad4 FIN exome AF: 0.00740

Gnomad4 NFE exome AF: 0.000822

Gnomad4 OTH exome AF: 0.000802

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74430

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00952

Gnomad4 NFE AF: 0.000883

Gnomad4 OTH AF: 0.00331

Bravo AF: 0.000854

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RBM12-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201181145; hg19: chr20-34240740;