Variant 7-134933217-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033138.4(CALD1):c.448G>A(p.Glu150Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000807 in 1,610,526 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

CALD1 (HGNC:1441): (caldesmon 1) This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca(2+)-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca(2+)-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

CALD1 links:

ENSG00000286458 (HGNC:):

ENSG00000286458 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059545815).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_033138.4 link	c.448G>A	p.Glu150Lys	missense_variant	Exon 5 of 15	ENST00000361675.7	NP_149129.2	Q05682-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7 link	c.448G>A	p.Glu150Lys	missense_variant	Exon 5 of 15	1	NM_033138.4	ENSP00000354826.2		Q05682-1

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

150970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

246460

Hom.:

AF XY:

0.000307

AC XY:

AN XY:

133620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00153

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000856

AC:

125

AN:

1459556

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

102

AN XY:

726040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000331

AC:

AN:

150970

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73588

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000882

Hom.:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448G>A (p.E150K) alteration is located in exon 5 (coding exon 3) of the CALD1 gene. This alteration results from a G to A substitution at nucleotide position 448, causing the glutamic acid (E) at amino acid position 150 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;.;T;.;.;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D;D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.060

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.6

M;.;M;M;M;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.035

D;D;D;T;D;D;D;D

Sift4G

Benign

0.17

T;T;T;T;T;T;T;T

Polyphen

0.45

B;.;.;P;B;B;B;.

Vest4

0.51

MutPred

0.60

Gain of ubiquitination at E150 (P = 0.0162);Gain of ubiquitination at E150 (P = 0.0162);Gain of ubiquitination at E150 (P = 0.0162);Gain of ubiquitination at E150 (P = 0.0162);Gain of ubiquitination at E150 (P = 0.0162);.;.;.;

MVP

0.53

MPC

0.17

ClinPred

0.10

GERP RS

5.4

Varity_R

0.16

gMVP

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over