Genetic Variant CALCOCO1:c.1006-96G>A (chr12-53716143-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020898.3(CALCOCO1):c.1006-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,579,508 control chromosomes in the GnomAD database, including 19,833 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1923 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17910 hom. )

Consequence

CALCOCO1
NM_020898.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110

Publications

9 publications found

Variant links:

Genes affected

CALCOCO1 (HGNC:29306): (calcium binding and coiled-coil domain 1) Enables several functions, including armadillo repeat domain binding activity; beta-catenin binding activity; and nuclear receptor coactivator activity. Involved in positive regulation of gene expression and positive regulation of transcription, DNA-templated. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CALCOCO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020898.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALCOCO1	NM_020898.3	MANE Select	c.1006-96G>A	intron	N/A	NP_065949.1
CALCOCO1	NM_001143682.2		c.751-96G>A	intron	N/A	NP_001137154.1
CALCOCO1	NR_026554.2		n.976-96G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALCOCO1	ENST00000550804.6	TSL:1 MANE Select	c.1006-96G>A	intron	N/A	ENSP00000449960.1
CALCOCO1	ENST00000548263.5	TSL:1	c.1006-96G>A	intron	N/A	ENSP00000447647.1
CALCOCO1	ENST00000943517.1		c.1006-96G>A	intron	N/A	ENSP00000613576.1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23487

AN:

152040

Hom.:

1925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.151

AC:

215140

AN:

1427348

Hom.:

17910

Cov.:

AF XY:

0.153

AC XY:

108552

AN XY:

708578

show subpopulations

African (AFR)

AF:

0.130

AC:

4235

AN:

32688

American (AMR)

AF:

0.131

AC:

5648

AN:

43106

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4373

AN:

24614

East Asian (EAS)

AF:

0.332

AC:

13096

AN:

39394

South Asian (SAS)

AF:

0.207

AC:

17152

AN:

82708

European-Finnish (FIN)

AF:

0.229

AC:

11206

AN:

48902

Middle Eastern (MID)

AF:

0.259

AC:

1435

AN:

5536

European-Non Finnish (NFE)

AF:

0.136

AC:

148009

AN:

1091378

Other (OTH)

AF:

0.169

AC:

9986

AN:

59022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

9465

18930

28395

37860

47325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5402

10804

16206

21608

27010

<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:

0.154

AC:

23490

AN:

152160

Hom.:

1923

Cov.:

AF XY:

0.160

AC XY:

11923

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.128

AC:

5316

AN:

41506

American (AMR)

AF:

0.136

AC:

2087

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

615

AN:

3468

East Asian (EAS)

AF:

0.315

AC:

1626

AN:

5168

South Asian (SAS)

AF:

0.206

AC:

994

AN:

4822

European-Finnish (FIN)

AF:

0.245

AC:

2588

AN:

10574

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9749

AN:

67996

Other (OTH)

AF:

0.177

AC:

375

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1024

2047

3071

4094

5118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.153

Hom.:

381

Bravo

AF:

0.146

Asia WGS

AF:

0.269

AC:

936

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.7

(source)

DANN

Benign

0.64

PhyloP100

-0.11

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

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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