rs11671131

chr19-46605228-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005184.4(CALM3):c.4-599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,800 control chromosomes in the GnomAD database, including 2,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2652 hom., cov: 33)
  • Exomes 𝑓: 0.16 (16 hom.)
• Consequence: CALM3 NM_005184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALM3	NM_005184.4	c.4-599T>C		intron_variant		ENST00000291295.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALM3	ENST00000291295.14	c.4-599T>C		intron_variant		1	NM_005184.4	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27302 AN: 152118 Hom.: 2656 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.163 AC: 92 AN: 564 Hom.: 16 Cov.: 0 AF XY: 0.179 AC XY: 53 AN XY: 296

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.179 AC: 27302 AN: 152236 Hom.: 2652 Cov.: 33 AF XY: 0.186 AC XY: 13810 AN XY: 74406

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.165

Alfa AF: 0.163 Hom.: 915

Bravo AF: 0.169

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.95
Dann	Benign	0.45

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: rs11671131; hg19: chr19-47108485;