Genetic Variant CALCOCO2:p.Val248Ala (chr17-48852546-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005831.5(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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1791 hom., cov: 32)

Exomes 𝑓: 0.052 ( 3657 hom. )

Consequence

CALCOCO2
NM_005831.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Publications

27 publications found

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:

ENSG00000293025 (HGNC:):

ENSG00000293025 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CALCOCO2	NM_005831.5 link	c.743T>C	p.Val248Ala	missense_variant	Exon 8 of 13	ENST00000258947.8	NP_005822.1	Q13137-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCOCO2	ENST00000258947.8 link	c.743T>C	p.Val248Ala	missense_variant	Exon 8 of 13	1	NM_005831.5	ENSP00000258947.3		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

GnomAD2 exomes

AF:

0.0739

AC:

18567

AN:

251120

AF XY:

0.0729

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 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

African (AFR)

AF:

0.286

AC:

9562

AN:

33418

American (AMR)

AF:

0.0643

AC:

2873

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

524

AN:

26120

East Asian (EAS)

AF:

0.0420

AC:

1665

AN:

39664

South Asian (SAS)

AF:

0.143

AC:

12341

AN:

86168

European-Finnish (FIN)

AF:

0.0576

AC:

3075

AN:

53418

Middle Eastern (MID)

AF:

0.0704

AC:

406

AN:

5764

European-Non Finnish (NFE)

AF:

0.0374

AC:

41487

AN:

1110756

Other (OTH)

AF:

0.0645

AC:

3890

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3127

6254

9381

12508

15635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1752

3504

5256

7008

8760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17330

AN:

152164

Hom.:

1791

Cov.:

AF XY:

0.114

AC XY:

8504

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.280

AC:

11614

AN:

41494

American (AMR)

AF:

0.0590

AC:

902

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

AN:

3468

East Asian (EAS)

AF:

0.0533

AC:

276

AN:

5182

South Asian (SAS)

AF:

0.151

AC:

727

AN:

4820

European-Finnish (FIN)

AF:

0.0639

AC:

677

AN:

10596

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0414

AC:

2814

AN:

67998

Other (OTH)

AF:

0.0805

AC:

170

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

696

1392

2089

2785

3481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0611

Hom.:

2743

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

(source)

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;.;.;.;.;.

PhyloP100

0.14

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

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.074

gMVP

0.059

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over