Variant 7-134933176-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033138.4(CALD1):c.407G>A(p.Arg136Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,612,926 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0056 ( 80 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032838583).

BP6

Variant 7-134933176-G-A is Benign according to our data. Variant chr7-134933176-G-A is described in ClinVar as [Benign]. Clinvar id is 770376.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00359 (543/151388) while in subpopulation SAS AF= 0.0286 (135/4718). AF 95% confidence interval is 0.0247. There are 7 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALD1	NM_033138.4 link	c.407G>A	p.Arg136Lys	missense_variant	5/15	ENST00000361675.7	NP_149129.2	Q05682-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7 link	c.407G>A	p.Arg136Lys	missense_variant	5/15	1	NM_033138.4	ENSP00000354826.2		Q05682-1

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

541

AN:

151270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000998

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00251

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.000665

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00630

AC:

1575

AN:

249930

Hom.:

AF XY:

0.00755

AC XY:

1021

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.00212

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.00380

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0301

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00457

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00564

AC:

8243

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4611

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0289

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00465

Gnomad4 OTH exome

AF:

0.00542

GnomAD4 genome

AF:

0.00359

AC:

543

AN:

151388

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

277

AN XY:

73914

show subpopulations

Gnomad4 AFR

AF:

0.000995

Gnomad4 AMR

AF:

0.00251

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.000665

Gnomad4 NFE

AF:

0.00449

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00280

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00704

AC:

855

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.12

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

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.80

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

MetaRNN

Benign

0.0033

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

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

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

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

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

REVEL

Benign

0.16

Sift

Benign

0.097

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

Sift4G

Benign

0.40

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

Polyphen

0.0030

B;.;.;B;B;B;B;.

Vest4

0.26

MVP

0.61

MPC

0.15

ClinPred

0.025

GERP RS

5.4

Varity_R

0.18

gMVP

0.056

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