rs12886752

Variant names:

• chr14-90397526-C-T
• rs12886752
• NM_006888.6:c.3+293C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006888.6(CALM1):​c.3+293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,428 control chromosomes in the GnomAD database, including 22,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22477 hom., cov: 31)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-90397526-C-T is Benign according to our data. Variant chr14-90397526-C-T is described in ClinVar as [Benign]. Clinvar id is 683300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM1	NM_006888.6	c.3+293C>T		intron_variant	Intron 1 of 5	ENST00000356978.9	NP_008819.1
CALM1	NM_001363669.2	c.-106+868C>T		intron_variant	Intron 1 of 5		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978.9	c.3+293C>T		intron_variant	Intron 1 of 5	1	NM_006888.6	ENSP00000349467.4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79022 AN: 151318 Hom.: 22473 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79044 AN: 151428 Hom.: 22477 Cov.: 31 AF XY: 0.524 AC XY: 38763 AN XY: 73992

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.539

Alfa AF: 0.528 Hom.: 3264

Bravo AF: 0.507

Asia WGS AF: 0.569 AC: 1971 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.87
CADD	Benign	7.7
DANN	Benign	0.94

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: rs12886752; hg19: chr14-90863870; COSMIC: COSV63663667; COSMIC: COSV63663667;