Genetic Variant ENST00000542996.7:c.269C>T (chr7-128754552-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000542996.7(CALU):c.269C>T(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,555,712 control chromosomes in the GnomAD database, including 96,989 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict 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 ( 6867 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90122 hom. )

Consequence

CALU
ENST00000542996.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.323

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=5.4627657E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALU	NM_001219.5 link	c.415+97C>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+97C>T		intron_variant	Intron 3 of 6	1	NM_001219.5	ENSP00000249364.4		O43852-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42132

AN:

151910

Hom.:

6863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0569

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.284

AC:

47226

AN:

166120

Hom.:

7676

AF XY:

0.289

AC XY:

25349

AN XY:

87660

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.0509

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.348

AC:

489163

AN:

1403684

Hom.:

90122

Cov.:

AF XY:

0.346

AC XY:

239616

AN XY:

693040

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.0547

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.277

AC:

42134

AN:

152028

Hom.:

6867

Cov.:

AF XY:

0.271

AC XY:

20137

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.0572

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.334

Hom.:

4772

Bravo

AF:

0.273

TwinsUK

AF:

0.378

AC:

1403

ALSPAC

AF:

0.378

AC:

1455

ESP6500AA

AF:

0.131

AC:

181

ESP6500EA

AF:

0.371

AC:

1182

ExAC

AF:

0.229

AC:

24022

Asia WGS

AF:

0.115

AC:

402

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.00055

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.12

Sift

Benign

0.26

T;T

Sift4G

Benign

0.30

T;T

Vest4

0.027

MPC

0.33

ClinPred

0.0011

GERP RS

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.26

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

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