rs3213718

Positions:

• chr14-90403569-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006888.6(CALM1):​c.179-293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 170,926 control chromosomes in the GnomAD database, including 22,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19477 hom., cov: 32)
  • Exomes 𝑓: 0.51 (2654 hom.)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.275

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-90403569-C-T is Benign according to our data. Variant chr14-90403569-C-T is described in ClinVar as [Benign]. Clinvar id is 668719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6	c.179-293C>T		intron_variant		ENST00000356978.9
CALM1	NM_001363669.2	c.71-293C>T		intron_variant
CALM1	NM_001363670.2	c.182-293C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9	c.179-293C>T		intron_variant		1	NM_006888.6	P1
	ENST00000555853.1	n.45-791G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75297 AN: 151840 Hom.: 19474 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.510 AC: 9672 AN: 18968 Hom.: 2654 AF XY: 0.511 AC XY: 5128 AN XY: 10028

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.496 AC: 75322 AN: 151958 Hom.: 19477 Cov.: 32 AF XY: 0.491 AC XY: 36432 AN XY: 74240

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.509

Alfa AF: 0.543 Hom.: 11165

Bravo AF: 0.481

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.65

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: rs3213718; hg19: chr14-90869913;