Variant rs2303015 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000258947.8(CALCOCO2):c.743T>C(p.Val248Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,612,440 control chromosomes in the GnomAD database, including 5,448 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1791 hom., cov: 32)

Exomes 𝑓: 0.052 ( 3657 hom. )

Consequence

CALCOCO2
ENST00000258947.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Variant links:

Genes affected

CALCOCO2 (HGNC:29912): (calcium binding and coiled-coil domain 2) This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a receptor for ubiquitin-coated bacteria and plays an important role in innate immunity by mediating macroautophagy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CALCOCO2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003417194).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCOCO2	NM_005831.5 linkuse as main transcript	c.743T>C	p.Val248Ala	missense_variant	8/13	ENST00000258947.8	NP_005822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCOCO2	ENST00000258947.8 linkuse as main transcript	c.743T>C	p.Val248Ala	missense_variant	8/13	1	NM_005831.5	ENSP00000258947	P1	Q13137-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17275

AN:

152046

Hom.:

1776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.0531

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0414

Gnomad OTH

AF:

0.0823

GnomAD3 exomes

AF:

0.0739

AC:

18567

AN:

251120

Hom.:

1266

AF XY:

0.0729

AC XY:

9897

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.0638

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.0600

Gnomad NFE exome

AF:

0.0400

Gnomad OTH exome

AF:

0.0566

GnomAD4 exome

AF:

0.0519

AC:

75823

AN:

1460276

Hom.:

3657

Cov.:

AF XY:

0.0539

AC XY:

39127

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.0643

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.0420

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0576

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0645

GnomAD4 genome

AF:

0.114

AC:

17330

AN:

152164

Hom.:

1791

Cov.:

AF XY:

0.114

AC XY:

8504

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.0590

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.0533

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0639

Gnomad4 NFE

AF:

0.0414

Gnomad4 OTH

AF:

0.0805

Alfa

AF:

0.0540

Hom.:

1114

Bravo

AF:

0.118

TwinsUK

AF:

0.0407

AC:

151

ALSPAC

AF:

0.0379

AC:

146

ESP6500AA

AF:

0.268

AC:

1183

ESP6500EA

AF:

0.0377

AC:

324

ExAC

AF:

0.0787

AC:

9555

Asia WGS

AF:

0.135

AC:

470

AN:

3478

EpiCase

AF:

0.0398

EpiControl

AF:

0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0032

T;.;.;.;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.65

T;T;T;T;T;T

MetaRNN

Benign

0.0034

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

M;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.11

T;T;T;D;T;D

Sift4G

Benign

0.81

T;T;T;T;T;T

Polyphen

0.095

B;.;.;.;.;.

Vest4

0.064

MPC

0.56

ClinPred

0.012

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.074

gMVP

0.059

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over