Genetic Variant CALU:c.582+133A>G (chr7-128759170-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001219.5(CALU):c.582+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 621,024 control chromosomes in the GnomAD database, including 499 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 0.039 ( 369 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 130 hom. )

Consequence

CALU
NM_001219.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.353

Publications

32 publications found

Variant links:

Genes affected

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

CALU 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALU	NM_001219.5	MANE Select	c.582+133A>G	intron	N/A	NP_001210.1
CALU	NM_001199671.2		c.606+133A>G	intron	N/A	NP_001186600.1
CALU	NM_001199672.2		c.606+133A>G	intron	N/A	NP_001186601.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALU	ENST00000249364.9	TSL:1 MANE Select	c.582+133A>G	intron	N/A	ENSP00000249364.4
CALU	ENST00000479257.5	TSL:1	c.606+133A>G	intron	N/A	ENSP00000420381.1
CALU	ENST00000542996.7	TSL:1	c.606+133A>G	intron	N/A	ENSP00000438248.1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5843

AN:

152130

Hom.:

356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0161

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0384

GnomAD4 exome

AF:

0.00587

AC:

2750

AN:

468776

Hom.:

130

AF XY:

0.00518

AC XY:

1240

AN XY:

239608

show subpopulations

African (AFR)

AF:

0.127

AC:

1414

AN:

11142

American (AMR)

AF:

0.0105

AC:

133

AN:

12710

Ashkenazi Jewish (ASJ)

AF:

0.00106

AC:

AN:

12284

East Asian (EAS)

AF:

0.0239

AC:

644

AN:

26934

South Asian (SAS)

AF:

0.00181

AC:

AN:

22698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35060

Middle Eastern (MID)

AF:

0.00849

AC:

AN:

1884

European-Non Finnish (NFE)

AF:

0.000533

AC:

171

AN:

320822

Other (OTH)

AF:

0.0126

AC:

318

AN:

25242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

120

240

359

479

599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.0387

AC:

5896

AN:

152248

Hom.:

369

Cov.:

AF XY:

0.0364

AC XY:

2713

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.130

AC:

5413

AN:

41490

American (AMR)

AF:

0.0163

AC:

249

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.0162

AC:

AN:

5192

South Asian (SAS)

AF:

0.00290

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68036

Other (OTH)

AF:

0.0384

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

269

539

808

1078

1347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0176

Hom.:

276

Bravo

AF:

0.0445

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.25

(source)

DANN

Benign

0.51

PhyloP100

0.35

PromoterAI

0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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