14-90397013-C-T

Position:

• chr14-90397013-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001363669.2(CALM1):​c.-106+355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 586,668 control chromosomes in the GnomAD database, including 72,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14991 hom., cov: 33)
  • Exomes 𝑓: 0.50 (57433 hom.)
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.315

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-90397013-C-T is Benign according to our data. Variant chr14-90397013-C-T is described in ClinVar as [Benign]. Clinvar id is 1164456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM1	NM_001363669.2	c.-106+355C>T		intron_variant			NP_001350598.1
CALM1	NM_006888.6	c.-218C>T		upstream_gene_variant		ENST00000356978.9	NP_008819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978.9	c.-218C>T		upstream_gene_variant		1	NM_006888.6	ENSP00000349467.4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61328 AN: 151836 Hom.: 14993 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.501 AC: 217872 AN: 434718 Hom.: 57433 Cov.: 3 AF XY: 0.496 AC XY: 114836 AN XY: 231530

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.404 AC: 61324 AN: 151950 Hom.: 14991 Cov.: 33 AF XY: 0.401 AC XY: 29774 AN XY: 74272

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.436

Alfa AF: 0.372 Hom.: 2102

Bravo AF: 0.379

Asia WGS AF: 0.262 AC: 909 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is associated with the following publications: (PMID: 15746150, 24205329) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Catecholaminergic polymorphic ventricular tachycardia 4;C4015671:Long QT syndrome 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.2
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs12885713; hg19: chr14-90863357;