Genetic Variant NM_005831.5:c.200G>A (chr17-48848083-G-A) – 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.200G>A(p.Arg67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,610,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CALCOCO2
NM_005831.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Publications

0 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 (REVEL=0.155).

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.200G>A	p.Arg67His	missense	Exon 3 of 13	NP_005822.1	Q13137-1
CALCOCO2	NM_001261395.2		c.-17G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_001248324.1	Q13137-5
CALCOCO2	NM_001261390.2		c.272G>A	p.Arg91His	missense	Exon 4 of 14	NP_001248319.1	Q13137-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALCOCO2	ENST00000258947.8	TSL:1 MANE Select	c.200G>A	p.Arg67His	missense	Exon 3 of 13	ENSP00000258947.3	Q13137-1
CALCOCO2	ENST00000508679.5	TSL:2	c.-17G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000423437.1	Q13137-5
CALCOCO2	ENST00000513119.5	TSL:5	c.-17G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	ENSP00000425090.1	D6REB0

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251136

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458694

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

725826

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33412

American (AMR)

AF:

0.000134

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109222

Other (OTH)

AF:

0.0000663

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.0000789

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41444

American (AMR)

AF:

0.000196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Benign

0.96

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.0063

PhyloP100

2.9

ClinPred

0.17

GERP RS

3.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.46

Mutation Taster

=68/32

polymorphism

(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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over