NM_001363669.2:c.-106+201G>T

Variant names:

• chr14-90396859-G-T
• rs7148581
• NM_001363669.2:c.-106+201G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363669.2(CALM1):​c.-106+201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 192,668 control chromosomes in the GnomAD database, including 6,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5026 hom., cov: 33)
  • Exomes 𝑓: 0.25 (1407 hom.)
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 14-90396859-G-T is Benign according to our data. Variant chr14-90396859-G-T is described in ClinVar as [Benign]. Clinvar id is 683288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALM1	NM_001363669.2	c.-106+201G>T		intron_variant	Intron 1 of 5		NP_001350598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALM1	ENST00000557020.5	c.-106+201G>T		intron_variant	Intron 1 of 4	4		ENSP00000451062.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38615 AN: 151928 Hom.: 5024 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.251 AC: 10202 AN: 40630 Hom.: 1407 AF XY: 0.254 AC XY: 5390 AN XY: 21244

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.0245

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.254 AC: 38639 AN: 152038 Hom.: 5026 Cov.: 33 AF XY: 0.251 AC XY: 18654 AN XY: 74332

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.247

Alfa AF: 0.142 Hom.: 272

Bravo AF: 0.255

Asia WGS AF: 0.179 AC: 622 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.044
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7148581; hg19: chr14-90863203;