Genetic Variant CALU:c.-11-86G>A (chr7-128748487-G-A) – 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.-11-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,206,580 control chromosomes in the GnomAD database, including 73,924 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 0.28 ( 6857 hom., cov: 33)

Exomes 𝑓: 0.34 ( 67067 hom. )

Consequence

CALU
NM_001219.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

7 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 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.-11-86G>A	intron	N/A	NP_001210.1
CALU	NM_001199671.2		c.14-86G>A	intron	N/A	NP_001186600.1
CALU	NM_001199672.2		c.14-86G>A	intron	N/A	NP_001186601.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CALU	ENST00000249364.9	TSL:1 MANE Select	c.-11-86G>A	intron	N/A	ENSP00000249364.4
CALU	ENST00000479257.5	TSL:1	c.14-86G>A	intron	N/A	ENSP00000420381.1
CALU	ENST00000542996.7	TSL:1	c.14-86G>A	intron	N/A	ENSP00000438248.1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42123

AN:

152048

Hom.:

6853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0685

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.345

AC:

363758

AN:

1054412

Hom.:

67067

Cov.:

AF XY:

0.342

AC XY:

181802

AN XY:

531442

show subpopulations

African (AFR)

AF:

0.134

AC:

3201

AN:

23812

American (AMR)

AF:

0.227

AC:

5743

AN:

25280

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

7743

AN:

20706

East Asian (EAS)

AF:

0.0616

AC:

2166

AN:

35188

South Asian (SAS)

AF:

0.207

AC:

13612

AN:

65704

European-Finnish (FIN)

AF:

0.281

AC:

12502

AN:

44510

Middle Eastern (MID)

AF:

0.388

AC:

1847

AN:

4766

European-Non Finnish (NFE)

AF:

0.383

AC:

302164

AN:

788462

Other (OTH)

AF:

0.321

AC:

14780

AN:

45984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11756

23512

35269

47025

58781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8382

16764

25146

33528

41910

<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:

0.277

AC:

42128

AN:

152168

Hom.:

6857

Cov.:

AF XY:

0.271

AC XY:

20141

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.141

AC:

5864

AN:

41526

American (AMR)

AF:

0.251

AC:

3835

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1317

AN:

3466

East Asian (EAS)

AF:

0.0693

AC:

359

AN:

5182

South Asian (SAS)

AF:

0.194

AC:

935

AN:

4824

European-Finnish (FIN)

AF:

0.287

AC:

3034

AN:

10584

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.376

AC:

25560

AN:

67982

Other (OTH)

AF:

0.303

AC:

638

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1500

3000

4501

6001

7501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.307

Hom.:

1008

Bravo

AF:

0.273

Asia WGS

AF:

0.121

AC:

422

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.44

(source)

DANN

Benign

0.38

PhyloP100

-0.51

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