19-46605665-G-A

Position:

• chr19-46605665-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005184.4(CALM3):​c.4-162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 152,356 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (38 hom., cov: 33)
• Consequence: CALM3 NM_005184.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-46605665-G-A is Benign according to our data. Variant chr19-46605665-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1217462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1987/152356) while in subpopulation AFR AF= 0.045 (1871/41582). AF 95% confidence interval is 0.0433. There are 38 homozygotes in gnomad4. There are 922 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1987 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM3	NM_005184.4	c.4-162G>A		intron_variant		ENST00000291295.14	NP_005175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM3	ENST00000291295.14	c.4-162G>A		intron_variant		1	NM_005184.4	ENSP00000291295.8

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1967 AN: 152238 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0130 AC: 1987 AN: 152356 Hom.: 38 Cov.: 33 AF XY: 0.0124 AC XY: 922 AN XY: 74510

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.00457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00895 Hom.: 1

Bravo AF: 0.0145

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.82

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: rs75486879; hg19: chr19-47108922;