Variant 19-46601421-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005184.4(CALM3):c.-14C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,504,984 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.016 ( 210 hom. )

Consequence

CALM3
NM_005184.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.742

Variant links:

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]

CALM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 19-46601421-C-A is Benign according to our data. Variant chr19-46601421-C-A is described in ClinVar as [Benign]. Clinvar id is 386525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-46601421-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0107 (1630/152270) while in subpopulation NFE AF= 0.0169 (1151/67988). AF 95% confidence interval is 0.0161. There are 17 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1630 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM3	NM_005184.4 link	c.-14C>A		5_prime_UTR_variant	1/6	ENST00000291295.14	NP_005175.2	P0DP23P0DP24P0DP25B4DJ51Q9BRL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM3	ENST00000291295 link	c.-14C>A		5_prime_UTR_variant	1/6	1	NM_005184.4	ENSP00000291295.8		P0DP25

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1630

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00566

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0122

AC:

1238

AN:

101626

Hom.:

AF XY:

0.0120

AC XY:

682

AN XY:

57068

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.00816

Gnomad ASJ exome

AF:

0.0346

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00624

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0155

AC:

20996

AN:

1352714

Hom.:

210

Cov.:

AF XY:

0.0154

AC XY:

10295

AN XY:

667880

show subpopulations

Gnomad4 AFR exome

AF:

0.00265

Gnomad4 AMR exome

AF:

0.00802

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00587

Gnomad4 FIN exome

AF:

0.00568

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0107

AC:

1630

AN:

152270

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

699

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00566

Gnomad4 NFE

AF:

0.0169

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 11, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 11, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over