Variant 14-90397145-G-A 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.-86G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,396,886 control chromosomes in the GnomAD database, including 502,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46624 hom., cov: 34)

Exomes 𝑓: 0.85 ( 455993 hom. )

Consequence

CALM1
NM_006888.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.74

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=-0.47).

BP6

Variant 14-90397145-G-A is Benign according to our data. Variant chr14-90397145-G-A is described in ClinVar as [Benign]. Clinvar id is 674613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6 linkuse as main transcript	c.-86G>A		5_prime_UTR_variant	1/6	ENST00000356978.9
CALM1	NM_001363669.2 linkuse as main transcript	c.-106+487G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9 linkuse as main transcript	c.-86G>A		5_prime_UTR_variant	1/6	1	NM_006888.6	P1

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117008

AN:

151910

Hom.:

46619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.790

Gnomad ASJ

AF:

0.828

Gnomad EAS

AF:

0.811

Gnomad SAS

AF:

0.758

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.785

GnomAD4 exome

AF:

0.855

AC:

1064107

AN:

1244864

Hom.:

455993

Cov.:

AF XY:

0.853

AC XY:

529360

AN XY:

620804

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.786

Gnomad4 ASJ exome

AF:

0.820

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.772

Gnomad4 FIN exome

AF:

0.846

Gnomad4 NFE exome

AF:

0.879

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.770

AC:

117051

AN:

152022

Hom.:

46624

Cov.:

AF XY:

0.769

AC XY:

57174

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.789

Gnomad4 ASJ

AF:

0.828

Gnomad4 EAS

AF:

0.811

Gnomad4 SAS

AF:

0.757

Gnomad4 FIN

AF:

0.847

Gnomad4 NFE

AF:

0.881

Gnomad4 OTH

AF:

0.784

Alfa

AF:

0.814

Hom.:

9538

Bravo

AF:

0.757

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.2

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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