Genetic Variant CALU:c.415+299C>T (chr7-128754754-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_001219.5(CALU):c.415+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 1,454,166 control chromosomes in the GnomAD database, including 1,972 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 0.046 ( 222 hom., cov: 31)

Exomes 𝑓: 0.050 ( 1750 hom. )

Consequence

CALU
NM_001219.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.594

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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.415+299C>T		intron_variant	Intron 3 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.415+299C>T		intron_variant	Intron 3 of 6	1	NM_001219.5	ENSP00000249364.4		O43852-1

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6930

AN:

151954

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.0638

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0417

GnomAD2 exomes

AF:

0.0617

AC:

7806

AN:

126470

AF XY:

0.0621

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.0777

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0683

Gnomad NFE exome

AF:

0.0440

Gnomad OTH exome

AF:

0.0604

GnomAD4 exome

AF:

0.0495

AC:

64457

AN:

1302094

Hom.:

1750

Cov.:

AF XY:

0.0502

AC XY:

32247

AN XY:

642320

show subpopulations

African (AFR)

AF:

0.0268

AC:

775

AN:

28868

American (AMR)

AF:

0.0746

AC:

2145

AN:

28750

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

472

AN:

22500

East Asian (EAS)

AF:

0.101

AC:

3552

AN:

35070

South Asian (SAS)

AF:

0.0751

AC:

5294

AN:

70498

European-Finnish (FIN)

AF:

0.0649

AC:

3133

AN:

48296

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

4708

European-Non Finnish (NFE)

AF:

0.0458

AC:

46246

AN:

1008906

Other (OTH)

AF:

0.0512

AC:

2791

AN:

54498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2924

5848

8773

11697

14621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1848

3696

5544

7392

9240

<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:

0.0456

AC:

6933

AN:

152072

Hom.:

222

Cov.:

AF XY:

0.0476

AC XY:

3537

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0258

AC:

1069

AN:

41484

American (AMR)

AF:

0.0570

AC:

871

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

660

AN:

5148

South Asian (SAS)

AF:

0.0854

AC:

412

AN:

4822

European-Finnish (FIN)

AF:

0.0638

AC:

673

AN:

10552

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0452

AC:

3076

AN:

68014

Other (OTH)

AF:

0.0450

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

338

677

1015

1354

1692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0449

Hom.:

Bravo

AF:

0.0443

Asia WGS

AF:

0.107

AC:

371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.0

(source)

DANN

Benign

0.81

PhyloP100

-0.59

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)

0.050

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