Genetic Variant CALCOCO2:p.Gln181Glu (chr17-48849375-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005831.5(CALCOCO2):c.541C>G(p.Gln181Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q181H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CALCOCO2
NM_005831.5 missense, splice_region

Scores

Splicing: ADA: 0.08790

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13981861).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005831.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALCOCO2	NM_005831.5	MANE Select	c.541C>G	p.Gln181Glu	missense splice_region	Exon 5 of 13	NP_005822.1	Q13137-1
CALCOCO2	NM_001261390.2		c.613C>G	p.Gln205Glu	missense splice_region	Exon 6 of 14	NP_001248319.1	Q13137-4
CALCOCO2	NM_001261391.2		c.604C>G	p.Gln202Glu	missense splice_region	Exon 6 of 14	NP_001248320.1	Q13137-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALCOCO2	ENST00000258947.8	TSL:1 MANE Select	c.541C>G	p.Gln181Glu	missense splice_region	Exon 5 of 13	ENSP00000258947.3	Q13137-1
CALCOCO2	ENST00000448105.7	TSL:2	c.613C>G	p.Gln205Glu	missense splice_region	Exon 6 of 14	ENSP00000398523.2	Q13137-4
CALCOCO2	ENST00000509507.5	TSL:2	c.604C>G	p.Gln202Glu	missense splice_region	Exon 6 of 14	ENSP00000424352.1	Q13137-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460440

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.0000224

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5114

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111556

Other (OTH)

AF:

0.0000332

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

M_CAP

Benign

0.0041

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

2.4

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

REVEL

Benign

0.043

Sift

Benign

0.11

Sift4G

Benign

0.39

Polyphen

0.0030

Vest4

0.17

MutPred

0.37

Gain of helix (P = 0.2294)

MVP

0.39

MPC

0.34

ClinPred

0.30

GERP RS

5.0

Varity_R

0.074

gMVP

0.14

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.088

dbscSNV1_RF

Benign

0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over