14-90397531-G-T

Variant names:

• chr14-90397531-G-T
• rs150215729
• NM_006888.6:c.3+298G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006888.6(CALM1):​c.3+298G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 151,392 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (199 hom., cov: 32)
• Consequence: CALM1 NM_006888.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-90397531-G-T is Benign according to our data. Variant chr14-90397531-G-T is described in ClinVar as Benign. ClinVar VariationId is 670032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0971 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.3+298G>T		intron	N/A	NP_008819.1	P0DP23
	CALM1	NM_001363669.2		c.-106+873G>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.3+298G>T		intron	N/A	ENSP00000349467.4	P0DP23
	CALM1	ENST00000971957.1		c.3+298G>T		intron	N/A	ENSP00000642016.1
	CALM1	ENST00000447653.8	TSL:2	c.-203+298G>T		intron	N/A	ENSP00000403491.4	Q96HY3

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5150 AN: 151284 Hom.: 201 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00376

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.0326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0340 AC: 5150 AN: 151392 Hom.: 199 Cov.: 32 AF XY: 0.0327 AC XY: 2414 AN XY: 73934

African (AFR) AF: 0.0997 AC: 4107 AN: 41198

American (AMR) AF: 0.0188 AC: 286 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3468

East Asian (EAS) AF: 0.000392 AC: 2 AN: 5096

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4806

European-Finnish (FIN) AF: 0.00376 AC: 39 AN: 10382

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.00688 AC: 467 AN: 67898

Other (OTH) AF: 0.0323 AC: 68 AN: 2108

Alfa AF: 0.0240 Hom.: 23

Bravo AF: 0.0381

Asia WGS AF: 0.0120 AC: 41 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.79
PhyloP100		-0.42
PromoterAI		0.043	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: rs150215729; hg19: chr14-90863875;