Genetic Variant CALD1:p.Glu320del (chr7-134933722-GGGA-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_033138.4(CALD1):c.957_959delGGA(p.Glu320del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00223 in 1,560,206 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 30)

Exomes 𝑓: 0.0019 ( 16 hom. )

Consequence

CALD1
NM_033138.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.87

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_033138.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 7-134933722-GGGA-G is Benign according to our data. Variant chr7-134933722-GGGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 774317.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 757 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_033138.4 link	c.957_959delGGA	p.Glu320del	disruptive_inframe_deletion	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.957_959delGGA	p.Glu320del	disruptive_inframe_deletion	Exon 5 of 15	1	NM_033138.4	ENSP00000354826.2		Q05682-1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

757

AN:

148088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00597

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00852

Gnomad OTH

AF:

0.00741

GnomAD2 exomes

AF:

0.00198

AC:

343

AN:

173432

AF XY:

0.00176

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000892

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00193

AC:

2730

AN:

1412002

Hom.:

AF XY:

0.00201

AC XY:

1401

AN XY:

697720

show subpopulations

Gnomad4 AFR exome

AF:

0.000527

AC:

AN:

32258

Gnomad4 AMR exome

AF:

0.00272

AC:

100

AN:

36708

Gnomad4 ASJ exome

AF:

0.000118

AC:

AN:

25334

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

36948

Gnomad4 SAS exome

AF:

0.0000746

AC:

AN:

80476

Gnomad4 FIN exome

AF:

0.00137

AC:

AN:

50418

Gnomad4 NFE exome

AF:

0.00217

AC:

2356

AN:

1085472

Gnomad4 Remaining exome

AF:

0.00305

AC:

179

AN:

58676

Heterozygous variant carriers

226

451

677

902

1128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00511

AC:

757

AN:

148204

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

310

AN XY:

71998

show subpopulations

Gnomad4 AFR

AF:

0.00169

AC:

0.00169356

AN:

0.00169356

Gnomad4 AMR

AF:

0.00596

AC:

0.00596394

AN:

0.00596394

Gnomad4 ASJ

AF:

0.000578

AC:

0.000578369

AN:

0.000578369

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00122

AC:

0.00121926

AN:

0.00121926

Gnomad4 NFE

AF:

0.00852

AC:

0.00851657

AN:

0.00851657

Gnomad4 OTH

AF:

0.00733

AC:

0.00733138

AN:

0.00733138

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00561

Hom.:

Bravo

AF:

0.00627

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=78/22

polymorphism

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