Genetic Variant CALU:c.221+123G>A (chr7-128748927-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001219.5(CALU):c.221+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 631,330 control chromosomes in the GnomAD database, including 1,039 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 0.047 ( 235 hom., cov: 33)

Exomes 𝑓: 0.052 ( 804 hom. )

Consequence

CALU
NM_001219.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.389

Publications

2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALU	NM_001219.5 link	c.221+123G>A		intron_variant	Intron 2 of 6	ENST00000249364.9	NP_001210.1	O43852-1Q6IAW5B3KQF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9 link	c.221+123G>A		intron_variant	Intron 2 of 6	1	NM_001219.5	ENSP00000249364.4		O43852-1

Frequencies

GnomAD3 genomes

AF:

0.0467

AC:

7106

AN:

152100

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0430

GnomAD4 exome

AF:

0.0524

AC:

25088

AN:

479112

Hom.:

804

AF XY:

0.0540

AC XY:

13518

AN XY:

250442

show subpopulations

African (AFR)

AF:

0.0268

AC:

349

AN:

13016

American (AMR)

AF:

0.0683

AC:

1070

AN:

15670

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

286

AN:

13772

East Asian (EAS)

AF:

0.0977

AC:

3022

AN:

30918

South Asian (SAS)

AF:

0.0924

AC:

3896

AN:

42182

European-Finnish (FIN)

AF:

0.0624

AC:

2105

AN:

33730

Middle Eastern (MID)

AF:

0.00986

AC:

AN:

3346

European-Non Finnish (NFE)

AF:

0.0434

AC:

13017

AN:

299744

Other (OTH)

AF:

0.0490

AC:

1310

AN:

26734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1119

2237

3356

4474

5593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<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:

0.0467

AC:

7112

AN:

152218

Hom.:

235

Cov.:

AF XY:

0.0490

AC XY:

3648

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0268

AC:

1111

AN:

41530

American (AMR)

AF:

0.0570

AC:

872

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

664

AN:

5176

South Asian (SAS)

AF:

0.112

AC:

539

AN:

4826

European-Finnish (FIN)

AF:

0.0637

AC:

674

AN:

10582

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3074

AN:

68022

Other (OTH)

AF:

0.0478

AC:

101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

348

696

1043

1391

1739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0440

Hom.:

Bravo

AF:

0.0448

Asia WGS

AF:

0.120

AC:

418

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

-0.39

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over