rs563916

Positions:

• chr17-48853545-G-A

Variant summary

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

The ENST00000258947.8(CALCOCO2):​c.912+533G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,234 control chromosomes in the GnomAD database, including 1,700 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 0.11 (1700 hom., cov: 33)
• Consequence: CALCOCO2 ENST00000258947.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

Genes affected

CALCOCO2 (HGNC:29912): (calcium binding and coiled-coil domain 2) This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a receptor for ubiquitin-coated bacteria and plays an important role in innate immunity by mediating macroautophagy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCOCO2	NM_005831.5	c.912+533G>A		intron_variant		ENST00000258947.8	NP_005822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCOCO2	ENST00000258947.8	c.912+533G>A		intron_variant		1	NM_005831.5	ENSP00000258947	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16349 AN: 152116 Hom.: 1697 Cov.: 33

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.107 AC: 16363 AN: 152234 Hom.: 1700 Cov.: 33 AF XY: 0.113 AC XY: 8401 AN XY: 74434

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.108

Alfa AF: 0.105 Hom.: 1411

Bravo AF: 0.105

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.71

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: rs563916; hg19: chr17-46930907;