NM_006888.6:c.179-293C>T

Variant names:

• chr14-90403569-C-T
• rs3213718
• NM_006888.6:c.179-293C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006888.6(CALM1):​c.179-293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 170,926 control chromosomes in the GnomAD database, including 22,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19477 hom., cov: 32)
  • Exomes 𝑓: 0.51 (2654 hom.)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.275
• Publications: 16 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

ENSG00000258424 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-90403569-C-T is Benign according to our data. Variant chr14-90403569-C-T is described in ClinVar as Benign. ClinVar VariationId is 668719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006888.6. 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_006888.6	MANE Select	c.179-293C>T		intron	N/A	NP_008819.1	P0DP23
	CALM1	NM_001363670.2		c.182-293C>T		intron	N/A	NP_001350599.1
	CALM1	NM_001363669.2		c.71-293C>T		intron	N/A	NP_001350598.1	Q96HY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM1	ENST00000356978.9	TSL:1 MANE Select	c.179-293C>T		intron	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000544280.6	TSL:1	c.71-293C>T		intron	N/A	ENSP00000442853.2	Q96HY3
	CALM1	ENST00000553964.5	TSL:1	n.2309-293C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75297 AN: 151840 Hom.: 19474 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.510 AC: 9672 AN: 18968 Hom.: 2654 AF XY: 0.511 AC XY: 5128 AN XY: 10028

African (AFR) AF: 0.380 AC: 263 AN: 692

American (AMR) AF: 0.349 AC: 224 AN: 642

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 398 AN: 742

East Asian (EAS) AF: 0.265 AC: 364 AN: 1372

South Asian (SAS) AF: 0.347 AC: 378 AN: 1088

European-Finnish (FIN) AF: 0.525 AC: 444 AN: 846

Middle Eastern (MID) AF: 0.500 AC: 53 AN: 106

European-Non Finnish (NFE) AF: 0.563 AC: 6912 AN: 12280

Other (OTH) AF: 0.530 AC: 636 AN: 1200

GnomAD4 genome AF: 0.496 AC: 75322 AN: 151958 Hom.: 19477 Cov.: 32 AF XY: 0.491 AC XY: 36432 AN XY: 74240

African (AFR) AF: 0.401 AC: 16625 AN: 41422

American (AMR) AF: 0.419 AC: 6403 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1170 AN: 5170

South Asian (SAS) AF: 0.427 AC: 2056 AN: 4818

European-Finnish (FIN) AF: 0.555 AC: 5848 AN: 10528

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39656 AN: 67964

Other (OTH) AF: 0.509 AC: 1071 AN: 2104

Alfa AF: 0.545 Hom.: 12546

Bravo AF: 0.481

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.28
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: rs3213718; hg19: chr14-90869913;