rs2300497

Variant names:

• chr14-90398939-T-C
• rs2300497
• ENST00000553964.5:n.1008T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-90398939-T-C
• chr14-90398939-T-G

Variant summary

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

The ENST00000553964.5(CALM1):​n.1008T>C variant causes a non coding transcript exon 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 ENST00000553964.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 15 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CALM1	NM_006888.6	c.4-1126T>C		intron_variant	Intron 1 of 5	ENST00000356978.9	NP_008819.1
CALM1	NM_001363670.2	c.-143T>C		5_prime_UTR_variant	Exon 1 of 6		NP_001350599.1
CALM1	NM_001363669.2	c.-105-1126T>C		intron_variant	Intron 1 of 5		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000356978.9	c.4-1126T>C		intron_variant	Intron 1 of 5	1	NM_006888.6	ENSP00000349467.4

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

African (AFR) AF: 0.541 AC: 6666 AN: 12318

American (AMR) AF: 0.753 AC: 3692 AN: 4904

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 4337 AN: 5214

East Asian (EAS) AF: 0.790 AC: 4009 AN: 5074

South Asian (SAS) AF: 0.754 AC: 18698 AN: 24806

European-Finnish (FIN) AF: 0.833 AC: 2633 AN: 3162

Middle Eastern (MID) AF: 0.753 AC: 2172 AN: 2884

European-Non Finnish (NFE) AF: 0.886 AC: 462128 AN: 521656

Other (OTH) AF: 0.840 AC: 16997 AN: 20244

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

African (AFR) AF: 0.569 AC: 23603 AN: 41452

American (AMR) AF: 0.791 AC: 12101 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2924 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4219 AN: 5174

South Asian (SAS) AF: 0.755 AC: 3633 AN: 4812

European-Finnish (FIN) AF: 0.845 AC: 8962 AN: 10606

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59856 AN: 68010

Other (OTH) AF: 0.786 AC: 1663 AN: 2116

Alfa AF: 0.851 Hom.: 28072

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
PhyloP100		-0.31
PromoterAI		-0.0072	Neutral
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: rs2300497; hg19: chr14-90865283;