19-46605754-T-C

Variant summary

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

The NM_005184.4(CALM3):c.4-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,503,128 control chromosomes in the GnomAD database, including 393,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45790 hom., cov: 34)
  • Exomes 𝑓: 0.71 (347697 hom.)
• Consequence: CALM3 NM_005184.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31

Genes affected

CALM3 (HGNC:1449): (calmodulin 3) This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-46605754-T-C is Benign according to our data. Variant chr19-46605754-T-C is described in ClinVar as [Benign]. Clinvar id is 678453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.4-73T>C		intron_variant		ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.4-73T>C		intron_variant		1	NM_005184.4	P1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116950 AN: 152080 Hom.: 45729 Cov.: 34

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.714 AC: 965223 AN: 1350930 Hom.: 347697 AF XY: 0.717 AC XY: 485829 AN XY: 677832

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.818

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.805

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.769 AC: 117073 AN: 152198 Hom.: 45790 Cov.: 34 AF XY: 0.773 AC XY: 57489 AN XY: 74398

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.774

Alfa AF: 0.736 Hom.: 5196

Bravo AF: 0.782

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

Long QT syndrome 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.18
Dann	Benign	0.20

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: rs3729510; hg19: chr19-47109011;