rs2300497

chr14-90398939-T-Cchr14-90398939-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.4-1126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 752,404 control chromosomes in the GnomAD database, including 274,829 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 0.78 (47193 hom., cov: 33)
  • Exomes 𝑓: 0.87 (227636 hom.)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6	c.4-1126T>C		intron_variant		ENST00000356978.9
CALM1	NM_001363670.2	c.-143T>C		5_prime_UTR_variant	1/6
CALM1	NM_001363669.2	c.-105-1126T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9	c.4-1126T>C		intron_variant		1	NM_006888.6	P1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118021 AN: 152024 Hom.: 47185 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.869 AC: 521332 AN: 600262 Hom.: 227636 Cov.: 8 AF XY: 0.867 AC XY: 249874 AN XY: 288198

Gnomad4 AFR exome AF: 0.541

Gnomad4 AMR exome AF: 0.753

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.886

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.776 AC: 118071 AN: 152142 Hom.: 47193 Cov.: 33 AF XY: 0.775 AC XY: 57675 AN XY: 74408

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.880

Gnomad4 OTH AF: 0.786

Alfa AF: 0.849 Hom.: 25170

Bravo AF: 0.763

Asia WGS AF: 0.751 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.3
Dann	Benign	0.52

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: rs2300497; hg19: chr14-90865283;