chr14-90396841-C-T

Variant names:

• chr14-90396841-C-T
• rs115788075
• NM_001363669.2:c.-106+183C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001363669.2(CALM1):​c.-106+183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 177,276 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (197 hom., cov: 32)
  • Exomes 𝑓: 0.012 (7 hom.)
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.197

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 14-90396841-C-T is Benign according to our data. Variant chr14-90396841-C-T is described in ClinVar as [Benign]. Clinvar id is 670029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM1	NM_001363669.2	c.-106+183C>T		intron_variant	Intron 1 of 5		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000557020.5	c.-106+183C>T		intron_variant	Intron 1 of 4	4		ENSP00000451062.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5145 AN: 152126 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00687

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0118 AC: 296 AN: 25038 Hom.: 7 AF XY: 0.0116 AC XY: 153 AN XY: 13170

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.00744

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0338 AC: 5145 AN: 152238 Hom.: 197 Cov.: 32 AF XY: 0.0324 AC XY: 2409 AN XY: 74436

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00687

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0242 Hom.: 21

Bravo AF: 0.0381

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.9
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115788075; hg19: chr14-90863185;