14-90397013-C-G

Variant names:

• chr14-90397013-C-G
• rs12885713
• NM_001363669.2:c.-106+355C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001363669.2(CALM1):​c.-106+355C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 42 publications found

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 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
• catecholaminergic polymorphic ventricular tachycardia 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	NM_001363669.2		c.-106+355C>G		intron	N/A	NP_001350598.1	Q96HY3
	CALM1	NM_006888.6	MANE Select	c.-218C>G		upstream_gene	N/A	NP_008819.1	P0DP23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	ENST00000557020.5	TSL:4	c.-106+355C>G		intron	N/A	ENSP00000451062.1	G3V361
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.-218C>G		upstream_gene	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000971957.1		c.-218C>G		upstream_gene	N/A	ENSP00000642016.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151916 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 435040 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 231702

African (AFR) AF: 0.00 AC: 0 AN: 9582

American (AMR) AF: 0.00 AC: 0 AN: 16468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12980

East Asian (EAS) AF: 0.00 AC: 0 AN: 27774

South Asian (SAS) AF: 0.00 AC: 0 AN: 45110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1922

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 266562

Other (OTH) AF: 0.00 AC: 0 AN: 25270

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151916 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74194

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67890

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 2433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.6
DANN	Benign	0.70
PhyloP100		-0.32
PromoterAI		-0.11	Neutral

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

Other links and lift over

dbSNP: rs12885713; hg19: chr14-90863357;