Variant chr20-35652764-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006047.6(RBM12):c.2559A>G(p.Pro853=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,612,590 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 63 hom. )

Consequence

RBM12
NM_006047.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.97

Variant links:

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]

RBM12 links:

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]

CPNE1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 20-35652764-T-C is Benign according to our data. Variant chr20-35652764-T-C is described in ClinVar as [Benign]. Clinvar id is 775434.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.97 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00671 (9791/1460238) while in subpopulation MID AF= 0.0347 (200/5760). AF 95% confidence interval is 0.0308. There are 63 homozygotes in gnomad4_exome. There are 4888 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 889 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM12	NM_006047.6 linkuse as main transcript	c.2559A>G	p.Pro853=	synonymous_variant	3/3	ENST00000374114.8
CPNE1	NM_152925.3 linkuse as main transcript	c.-1+11996A>G		intron_variant		ENST00000397443.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM12	ENST00000374114.8 linkuse as main transcript	c.2559A>G	p.Pro853=	synonymous_variant	3/3	1	NM_006047.6	P1
CPNE1	ENST00000397443.7 linkuse as main transcript	c.-1+11996A>G		intron_variant		5	NM_152925.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

891

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00732

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00660

AC:

1635

AN:

247842

Hom.:

AF XY:

0.00667

AC XY:

897

AN XY:

134538

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00217

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00767

Gnomad OTH exome

AF:

0.00876

GnomAD4 exome

AF:

0.00671

AC:

9791

AN:

1460238

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

4888

AN XY:

726296

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00265

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.00671

Gnomad4 OTH exome

AF:

0.00794

GnomAD4 genome

AF:

0.00584

AC:

889

AN:

152352

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

449

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.00733

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00803

Hom.:

Bravo

AF:

0.00567

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over