14-90396869-G-A

Variant names:

• chr14-90396869-G-A
• rs559185449
• NM_001363669.2:c.-106+211G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363669.2(CALM1):​c.-106+211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 54,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

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+211G>A		intron	N/A	NP_001350598.1	Q96HY3
	CALM1	NM_006888.6	MANE Select	c.-362G>A		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+211G>A		intron	N/A	ENSP00000451062.1	G3V361
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.-362G>A		upstream_gene	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000971957.1		c.-362G>A		upstream_gene	N/A	ENSP00000642016.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000183 AC: 1 AN: 54664 Hom.: 0 AF XY: 0.0000355 AC XY: 1 AN XY: 28206

African (AFR) AF: 0.00 AC: 0 AN: 1760

American (AMR) AF: 0.00 AC: 0 AN: 1448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2010

East Asian (EAS) AF: 0.00 AC: 0 AN: 3384

South Asian (SAS) AF: 0.00179 AC: 1 AN: 558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36474

Other (OTH) AF: 0.00 AC: 0 AN: 3822

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.6
DANN	Benign	0.82
PhyloP100		0.063
PromoterAI		-0.072	Neutral

Splicing

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

Other links and lift over

dbSNP: rs559185449; hg19: chr14-90863213;