Variant 14-90396859-G-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_001363669.2(CALM1):c.-106+201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 192,668 control chromosomes in the GnomAD database, including 6,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5026 hom., cov: 33)

Exomes 𝑓: 0.25 ( 1407 hom. )

Consequence

CALM1
NM_001363669.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.18

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=-0.51).

BP6

Variant 14-90396859-G-T is Benign according to our data. Variant chr14-90396859-G-T is described in ClinVar as [Benign]. Clinvar id is 683288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_001363669.2 linkuse as main transcript	c.-106+201G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000557020.5 linkuse as main transcript	c.-106+201G>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38615

AN:

151928

Hom.:

5024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.0335

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.251

AC:

10202

AN:

40630

Hom.:

1407

AF XY:

0.254

AC XY:

5390

AN XY:

21244

show subpopulations

Gnomad4 AFR exome

AF:

0.288

Gnomad4 AMR exome

AF:

0.276

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.0245

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.254

AC:

38639

AN:

152038

Hom.:

5026

Cov.:

AF XY:

0.251

AC XY:

18654

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.0338

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.142

Hom.:

272

Bravo

AF:

0.255

Asia WGS

AF:

0.179

AC:

622

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 19, 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

-0.51

CADD

Benign

0.044

DANN

Benign

0.42

Splicing

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