Variant chr14-90400002-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006888.6(CALM1):c.4-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,179,520 control chromosomes in the GnomAD database, including 218,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21875 hom., cov: 33)

Exomes 𝑓: 0.61 ( 196927 hom. )

Consequence

CALM1
NM_006888.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0710

Variant links:

Genes affected

CALM1 (HGNC:1442): (calmodulin 1) This gene encodes one of three calmodulin proteins which are members of the EF-hand calcium-binding protein family. Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. Two pseudogenes have been identified on chromosome 7 and X. Multiple transcript variants encoding different isoforms have been found for this gene.A missense mutation in the CALM1 gene has been associated with ventricular tachycardia.[provided by RefSeq, May 2020]

CALM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 14-90400002-C-T is Benign according to our data. Variant chr14-90400002-C-T is described in ClinVar as [Benign]. Clinvar id is 674614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CALM1	NM_006888.6 linkuse as main transcript	c.4-63C>T	intron_variant	ENST00000356978.9
CALM1	NM_001363669.2 linkuse as main transcript	c.-105-63C>T	intron_variant
CALM1	NM_001363670.2 linkuse as main transcript	c.7-63C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9 linkuse as main transcript	c.4-63C>T		intron_variant		1	NM_006888.6	P1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76625

AN:

151938

Hom.:

21873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.612

AC:

628445

AN:

1027464

Hom.:

196927

Cov.:

AF XY:

0.608

AC XY:

322012

AN XY:

529570

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.587

Gnomad4 EAS exome

AF:

0.785

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.504

AC:

76645

AN:

152056

Hom.:

21875

Cov.:

AF XY:

0.507

AC XY:

37661

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.505

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.593

Hom.:

26947

Bravo

AF:

0.487

Asia WGS

AF:

0.561

AC:

1950

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Catecholaminergic polymorphic ventricular tachycardia 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.7

DANN

Benign

0.56

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