Variant rs2290228 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001219.5(CALU):c.11G>A(p.Arg4Gln) variant causes a missense change. The variant allele was found at a frequency of 0.159 in 1,612,570 control chromosomes in the GnomAD database, including 21,307 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1786 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19521 hom. )

Consequence

CALU
NM_001219.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.20

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001409024).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALU	NM_001219.5 link	c.11G>A	p.Arg4Gln	missense_variant	2/7	ENST00000249364.9	NP_001210.1	O43852-1Q6IAW5B3KQF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9 link	c.11G>A	p.Arg4Gln	missense_variant	2/7	1	NM_001219.5	ENSP00000249364.4		O43852-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22358

AN:

152046

Hom.:

1787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.167

AC:

41916

AN:

251026

Hom.:

3824

AF XY:

0.170

AC XY:

23114

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.216

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.160

AC:

233449

AN:

1460406

Hom.:

19521

Cov.:

AF XY:

0.162

AC XY:

117728

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.147

AC:

22365

AN:

152164

Hom.:

1786

Cov.:

AF XY:

0.147

AC XY:

10907

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.159

Hom.:

4291

Bravo

AF:

0.147

TwinsUK

AF:

0.156

AC:

578

ALSPAC

AF:

0.155

AC:

597

ESP6500AA

AF:

0.110

AC:

485

ESP6500EA

AF:

0.165

AC:

1415

ExAC

AF:

0.168

AC:

20430

Asia WGS

AF:

0.217

AC:

756

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;T;.;.

Eigen

Benign

0.067

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.050

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.39

T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.0030

.;.;B;.;.

Vest4

0.086

MPC

0.38

ClinPred

0.016

GERP RS

5.9

Varity_R

0.15

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over