dbSNP rs2290227: 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:

Genome browser will be placed here

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.

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	UniProt
CALU	NM_001219.5	MANE Select	c.221+123G>A	intron	N/A	NP_001210.1	Q6IAW5
CALU	NM_001199671.2		c.245+123G>A	intron	N/A	NP_001186600.1	O43852-3
CALU	NM_001199672.2		c.245+123G>A	intron	N/A	NP_001186601.1	O43852-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALU	ENST00000249364.9	TSL:1 MANE Select	c.221+123G>A	intron	N/A	ENSP00000249364.4	O43852-1
CALU	ENST00000479257.5	TSL:1	c.245+123G>A	intron	N/A	ENSP00000420381.1	O43852-3
CALU	ENST00000542996.7	TSL:1	c.245+123G>A	intron	N/A	ENSP00000438248.1	O43852-4

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over