17-48862296-C-G

Variant names:

• chr17-48862296-C-G
• rs10278
• NM_005831.5:c.1165C>G

Variant summary

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

The NM_005831.5(CALCOCO2):​c.1165C>G​(p.Pro389Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,573,920 control chromosomes in the GnomAD database, including 73,641 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8064 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65577 hom.)
• Consequence: CALCOCO2 NM_005831.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 45 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 (MetaRNN=0.0048308074).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCOCO2	NM_005831.5	c.1165C>G	p.Pro389Ala	missense_variant	Exon 12 of 13	ENST00000258947.8	NP_005822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCOCO2	ENST00000258947.8	c.1165C>G	p.Pro389Ala	missense_variant	Exon 12 of 13	1	NM_005831.5	ENSP00000258947.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48593 AN: 151824 Hom.: 8051 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.307 AC: 76803 AN: 250426 AF XY: 0.301

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.442

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.298 AC: 423620 AN: 1421978 Hom.: 65577 Cov.: 28 AF XY: 0.296 AC XY: 210165 AN XY: 709636

African (AFR) AF: 0.344 AC: 11186 AN: 32534

American (AMR) AF: 0.439 AC: 19445 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10089 AN: 25826

East Asian (EAS) AF: 0.180 AC: 7125 AN: 39568

South Asian (SAS) AF: 0.248 AC: 21154 AN: 85430

European-Finnish (FIN) AF: 0.277 AC: 14787 AN: 53384

Middle Eastern (MID) AF: 0.371 AC: 2099 AN: 5664

European-Non Finnish (NFE) AF: 0.297 AC: 319388 AN: 1076252

Other (OTH) AF: 0.311 AC: 18347 AN: 59010

GnomAD4 genome AF: 0.320 AC: 48644 AN: 151942 Hom.: 8064 Cov.: 32 AF XY: 0.321 AC XY: 23847 AN XY: 74264

African (AFR) AF: 0.336 AC: 13898 AN: 41406

American (AMR) AF: 0.441 AC: 6719 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1390 AN: 3472

East Asian (EAS) AF: 0.163 AC: 842 AN: 5160

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2845 AN: 10546

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20853 AN: 67974

Other (OTH) AF: 0.324 AC: 683 AN: 2108

Alfa AF: 0.298 Hom.: 5313

Bravo AF: 0.334

TwinsUK AF: 0.302 AC: 1120

ALSPAC AF: 0.309 AC: 1191

ESP6500AA AF: 0.335 AC: 1475

ESP6500EA AF: 0.302 AC: 2601

ExAC AF: 0.299 AC: 36342

Asia WGS AF: 0.208 AC: 725 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.0
DANN	Benign	0.89
DEOGEN2	Benign	0.0010	T;.;.;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.74	T;T;T;T;T
MetaRNN	Benign	0.0048	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PhyloP100		0.023
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Benign	0.21	T;D;D;T;T
Polyphen		0.0060	B;.;.;.;.
Vest4		0.11
MPC		0.23
ClinPred		0.0015	T
GERP RS		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.34
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10278; hg19: chr17-46939658; COSMIC: COSV51953043; COSMIC: COSV51953043;