Variant 7-134933281-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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, single submitter B:1

Conservation

PhyloP100: 3.71

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 773905.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALD1	NM_033138.4 linkuse as main transcript	c.512C>T	p.Ser171Phe	missense_variant	5/15	ENST00000361675.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALD1	ENST00000361675.7 linkuse as main transcript	c.512C>T	p.Ser171Phe	missense_variant	5/15	1	NM_033138.4		Q05682-1
	ENST00000665703.1 linkuse as main transcript	n.71+64802G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.00367

AC:

877

AN:

239024

Hom.:

AF XY:

0.00274

AC XY:

355

AN XY:

129602

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 SAS exome

AF:

0.000173

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

Gnomad4 AFR exome

AF:

0.0495

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.0146

AC:

2034

AN:

139754

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

953

AN XY:

67410

show subpopulations

Gnomad4 AFR

AF:

0.0520

Gnomad4 AMR

AF:

0.00446

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000201

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00250

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

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0039

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

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

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

MutationTaster

Benign

0.99

D;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.9

D;D;D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.018

D;D;D;D;D;D;D;D

Polyphen

0.85

P;.;.;D;P;P;P;.

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

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