rs563916

Variant names:

• chr17-48853545-G-A
• rs563916
• NM_005831.5:c.912+533G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005831.5(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 NM_005831.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• Publications: 7 publications found

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]

ENSG00000293025 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005831.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO2	NM_005831.5	MANE Select	c.912+533G>A		intron	N/A	NP_005822.1
	CALCOCO2	NM_001261390.2		c.984+533G>A		intron	N/A	NP_001248319.1
	CALCOCO2	NM_001261391.2		c.975+533G>A		intron	N/A	NP_001248320.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO2	ENST00000258947.8	TSL:1 MANE Select	c.912+533G>A		intron	N/A	ENSP00000258947.3
	CALCOCO2	ENST00000448105.7	TSL:2	c.984+533G>A		intron	N/A	ENSP00000398523.2
	CALCOCO2	ENST00000509507.5	TSL:2	c.975+533G>A		intron	N/A	ENSP00000424352.1

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

African (AFR) AF: 0.0253 AC: 1050 AN: 41558

American (AMR) AF: 0.133 AC: 2036 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3013 AN: 5170

South Asian (SAS) AF: 0.158 AC: 763 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1780 AN: 10586

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7013 AN: 68006

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.104 Hom.: 1999

Bravo AF: 0.105

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.71
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs563916; hg19: chr17-46930907;