chr14-90397145-G-A

Variant names:

• chr14-90397145-G-A
• rs12886342
• NM_006888.6:c.-86G>A

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.-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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.74

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 -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 rank	MANE	Protein	UniProt
CALM1	NM_006888.6	c.-86G>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000356978.9	NP_008819.1
CALM1	NM_001363669.2	c.-106+487G>A		intron_variant	Intron 1 of 5		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978	c.-86G>A		5_prime_UTR_variant	Exon 1 of 6	1	NM_006888.6	ENSP00000349467.4

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117008 AN: 151910 Hom.: 46619 Cov.: 34

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.: 17 AF XY: 0.853 AC XY: 529360 AN XY: 620804

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.: 34 AF XY: 0.769 AC XY: 57174 AN XY: 74328

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 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. -

Catecholaminergic polymorphic ventricular tachycardia 4 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs12886342; hg19: chr14-90863489; COSMIC: COSV63663037; COSMIC: COSV63663037;