rs2300501

Positions:

• chr14-90399471-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006888.6(CALM1):​c.4-594C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 152,792 control chromosomes in the GnomAD database, including 1,410 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 0.094 (1408 hom., cov: 33)
  • Exomes 𝑓: 0.082 (2 hom.)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6	c.4-594C>G		intron_variant		ENST00000356978.9
CALM1	NM_001363669.2	c.-105-594C>G		intron_variant
CALM1	NM_001363670.2	c.6+384C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9	c.4-594C>G		intron_variant		1	NM_006888.6	P1

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14257 AN: 152140 Hom.: 1414 Cov.: 33

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0908

GnomAD4 exome AF: 0.0824 AC: 44 AN: 534 Hom.: 2 Cov.: 0 AF XY: 0.0756 AC XY: 31 AN XY: 410

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0486

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0937 AC: 14259 AN: 152258 Hom.: 1408 Cov.: 33 AF XY: 0.0992 AC XY: 7386 AN XY: 74434

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0913

Alfa AF: 0.0719 Hom.: 58

Bravo AF: 0.101

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.6
DANN	Benign	0.67

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: rs2300501; hg19: chr14-90865815;