chr14-90406669-T-G

Variant names:

• chr14-90406669-T-G
• rs3814843
• NM_006888.6:c.*1952T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006888.6(CALM1):​c.*1952T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 152,434 control chromosomes in the GnomAD database, including 151 homozygotes. 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 0.039 (150 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1 hom.)
• Consequence: CALM1 NM_006888.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 21 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• catecholaminergic polymorphic ventricular tachycardia

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006888.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	NM_006888.6	MANE Select	c.*1952T>G		3_prime_UTR	Exon 6 of 6	NP_008819.1
	CALM1	NM_001363670.2		c.*1952T>G		3_prime_UTR	Exon 6 of 6	NP_001350599.1
	CALM1	NM_001363669.2		c.*1952T>G		3_prime_UTR	Exon 6 of 6	NP_001350598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.*1952T>G		3_prime_UTR	Exon 6 of 6	ENSP00000349467.4

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5867 AN: 152186 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0615 AC: 8 AN: 130 Hom.: 1 Cov.: 0 AF XY: 0.0652 AC XY: 6 AN XY: 92

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0667 AC: 2 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0698 AC: 6 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0386 AC: 5876 AN: 152304 Hom.: 150 Cov.: 32 AF XY: 0.0394 AC XY: 2932 AN XY: 74470

African (AFR) AF: 0.0181 AC: 753 AN: 41580

American (AMR) AF: 0.0380 AC: 581 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.0893 AC: 463 AN: 5186

South Asian (SAS) AF: 0.0786 AC: 379 AN: 4824

European-Finnish (FIN) AF: 0.0417 AC: 443 AN: 10616

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0423 AC: 2875 AN: 68012

Other (OTH) AF: 0.0535 AC: 113 AN: 2114

Alfa AF: 0.0416 Hom.: 238

Bravo AF: 0.0367

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.7
DANN	Benign	0.87
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3814843; hg19: chr14-90873013;