14-90406669-T-G

Position:

• chr14-90406669-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM1	NM_006888.6	c.*1952T>G		3_prime_UTR_variant	6/6	ENST00000356978.9	NP_008819.1
CALM1	NM_001363670.2	c.*1952T>G		3_prime_UTR_variant	6/6		NP_001350599.1
CALM1	NM_001363669.2	c.*1952T>G		3_prime_UTR_variant	6/6		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978.9	c.*1952T>G		3_prime_UTR_variant	6/6	1	NM_006888.6	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

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.0698

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.0786

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0414 Hom.: 164

Bravo AF: 0.0367

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.7
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs3814843; hg19: chr14-90873013;