14-90397531-G-T

Position:

• chr14-90397531-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_006888.6	c.3+298G>T		intron_variant		ENST00000356978.9
CALM1	NM_001363669.2	c.-106+873G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000356978.9	c.3+298G>T		intron_variant		1	NM_006888.6	P1

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

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00376

Gnomad4 NFE AF: 0.00688

Gnomad4 OTH AF: 0.0323

Alfa AF: 0.0210 Hom.: 18

Bravo AF: 0.0381

Asia WGS AF: 0.0120 AC: 41 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-0.86
CADD	Benign	6.8
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs150215729; hg19: chr14-90863875;