Variant chr17-48862296-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005831.5(CALCOCO2):c.1165C>G(p.Pro389Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,573,920 control chromosomes in the GnomAD database, including 73,641 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.32 ( 8064 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65577 hom. )

Consequence

CALCOCO2
NM_005831.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0230

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=0.0048308074).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCOCO2	NM_005831.5 linkuse as main transcript	c.1165C>G	p.Pro389Ala	missense_variant	12/13	ENST00000258947.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCOCO2	ENST00000258947.8 linkuse as main transcript	c.1165C>G	p.Pro389Ala	missense_variant	12/13	1	NM_005831.5	P1	Q13137-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48593

AN:

151824

Hom.:

8051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.307

AC:

76803

AN:

250426

Hom.:

12637

AF XY:

0.301

AC XY:

40733

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.298

AC:

423620

AN:

1421978

Hom.:

65577

Cov.:

AF XY:

0.296

AC XY:

210165

AN XY:

709636

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.297

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.320

AC:

48644

AN:

151942

Hom.:

8064

Cov.:

AF XY:

0.321

AC XY:

23847

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.307

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.298

Hom.:

5313

Bravo

AF:

0.334

TwinsUK

AF:

0.302

AC:

1120

ALSPAC

AF:

0.309

AC:

1191

ESP6500AA

AF:

0.335

AC:

1475

ESP6500EA

AF:

0.302

AC:

2601

ExAC

AF:

0.299

AC:

36342

Asia WGS

AF:

0.208

AC:

725

AN:

3478

EpiCase

AF:

0.320

EpiControl

AF:

0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.0

DANN

Benign

0.89

DEOGEN2

Benign

0.0010

T;.;.;.;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

T;T;T;T;T

MetaRNN

Benign

0.0048

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.21

T;D;D;T;T

Polyphen

0.0060

B;.;.;.;.

Vest4

0.11

MPC

0.23

ClinPred

0.0015

GERP RS

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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