14-90396691-G-T

Position:

• chr14-90396691-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001363669.2(CALM1):​c.-106+33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 152,286 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CALM1 NM_001363669.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.459

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 14-90396691-G-T is Benign according to our data. Variant chr14-90396691-G-T is described in ClinVar as [Benign]. Clinvar id is 673493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM1	NM_001363669.2	c.-106+33G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM1	ENST00000557020.5	c.-106+33G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2727 AN: 152168 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00862

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 342 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 256

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0180 AC: 2734 AN: 152286 Hom.: 80 Cov.: 32 AF XY: 0.0175 AC XY: 1303 AN XY: 74458

Gnomad4 AFR AF: 0.0629

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0202

Asia WGS AF: 0.00808 AC: 28 AN: 3478

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 16, 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	-0.41
CADD	Benign	7.1
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116407419; hg19: chr14-90863035;