rs114442219

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033138.4(CALD1):c.512C>T(p.Ser171Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00263 in 1,595,466 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 37 hom., cov: 29)

Exomes 𝑓: 0.0015 ( 42 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.71

Publications

6 publications found

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039254725).

BP6

Variant 7-134933281-C-T is Benign according to our data. Variant chr7-134933281-C-T is described in ClinVar as Benign. ClinVar VariationId is 773905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033138.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CALD1	NM_033138.4	MANE Select	c.512C>T	p.Ser171Phe	missense	Exon 5 of 15	NP_149129.2
CALD1	NM_001438765.1		c.512C>T	p.Ser171Phe	missense	Exon 5 of 15	NP_001425694.1
CALD1	NM_001438766.1		c.494C>T	p.Ser165Phe	missense	Exon 3 of 13	NP_001425695.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALD1	ENST00000361675.7	TSL:1 MANE Select	c.512C>T	p.Ser171Phe	missense	Exon 5 of 15	ENSP00000354826.2	Q05682-1
CALD1	ENST00000393118.7	TSL:1	c.494C>T	p.Ser165Phe	missense	Exon 3 of 13	ENSP00000376826.2	Q05682-3
CALD1	ENST00000361901.6	TSL:1	c.512C>T	p.Ser171Phe	missense	Exon 5 of 14	ENSP00000354513.2	Q05682-4

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2031

AN:

139638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00454

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00338

Gnomad NFE

AF:

0.000201

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00367

AC:

877

AN:

239024

AF XY:

0.00274

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.00244

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00148

AC:

2157

AN:

1455712

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

977

AN XY:

723728

show subpopulations

African (AFR)

AF:

0.0495

AC:

1634

AN:

33010

American (AMR)

AF:

0.00275

AC:

122

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39070

South Asian (SAS)

AF:

0.000153

AC:

AN:

84970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000167

AC:

185

AN:

1109106

Other (OTH)

AF:

0.00298

AC:

179

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0146

AC:

2034

AN:

139754

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

953

AN XY:

67410

show subpopulations

African (AFR)

AF:

0.0520

AC:

1938

AN:

37254

American (AMR)

AF:

0.00446

AC:

AN:

13240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3298

East Asian (EAS)

AF:

0.00

AC:

AN:

4886

South Asian (SAS)

AF:

0.00

AC:

AN:

4126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9046

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.000201

AC:

AN:

64804

Other (OTH)

AF:

0.0119

AC:

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00514

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0483

AC:

213

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

PhyloP100

3.7

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.018

Polyphen

0.85

Vest4

0.58

MVP

0.42

MPC

0.16

ClinPred

0.031

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.17

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over