rs12885713

Variant names:

• chr14-90397013-C-T
• rs12885713
• NM_001363669.2:c.-106+355C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-90397013-C-T
• chr14-90397013-C-A
• chr14-90397013-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001363669.2(CALM1):​c.-106+355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 586,668 control chromosomes in the GnomAD database, including 72,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14991 hom., cov: 33)
  • Exomes 𝑓: 0.50 (57433 hom.)
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.315
• Publications: 42 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• catecholaminergic polymorphic ventricular tachycardia

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-90397013-C-T is Benign according to our data. Variant chr14-90397013-C-T is described in ClinVar as Benign. ClinVar VariationId is 1164456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	NM_001363669.2		c.-106+355C>T		intron	N/A	NP_001350598.1	Q96HY3
	CALM1	NM_006888.6	MANE Select	c.-218C>T		upstream_gene	N/A	NP_008819.1	P0DP23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	ENST00000557020.5	TSL:4	c.-106+355C>T		intron	N/A	ENSP00000451062.1	G3V361
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.-218C>T		upstream_gene	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000971957.1		c.-218C>T		upstream_gene	N/A	ENSP00000642016.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61328 AN: 151836 Hom.: 14993 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.501 AC: 217872 AN: 434718 Hom.: 57433 Cov.: 3 AF XY: 0.496 AC XY: 114836 AN XY: 231530

African (AFR) AF: 0.151 AC: 1444 AN: 9578

American (AMR) AF: 0.359 AC: 5903 AN: 16448

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 6356 AN: 12962

East Asian (EAS) AF: 0.282 AC: 7832 AN: 27758

South Asian (SAS) AF: 0.400 AC: 18040 AN: 45100

European-Finnish (FIN) AF: 0.537 AC: 15756 AN: 29354

Middle Eastern (MID) AF: 0.435 AC: 835 AN: 1920

European-Non Finnish (NFE) AF: 0.561 AC: 149432 AN: 266360

Other (OTH) AF: 0.486 AC: 12274 AN: 25238

GnomAD4 genome AF: 0.404 AC: 61324 AN: 151950 Hom.: 14991 Cov.: 33 AF XY: 0.401 AC XY: 29774 AN XY: 74272

African (AFR) AF: 0.139 AC: 5765 AN: 41500

American (AMR) AF: 0.374 AC: 5713 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1057 AN: 5130

South Asian (SAS) AF: 0.390 AC: 1883 AN: 4824

European-Finnish (FIN) AF: 0.532 AC: 5628 AN: 10572

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.561 AC: 38067 AN: 67854

Other (OTH) AF: 0.436 AC: 920 AN: 2110

Alfa AF: 0.364 Hom.: 2433

Bravo AF: 0.379

Asia WGS AF: 0.262 AC: 909 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 4;C4015671:Long QT syndrome 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.2
DANN	Benign	0.86
PhyloP100		-0.32
PromoterAI		-0.15	Neutral
Mutation Taster		=300/0	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: rs12885713; hg19: chr14-90863357;