chr17-48852546-T-C

Position:

• chr17-48852546-T-C

Variant summary

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

The NM_005831.5(CALCOCO2):​c.743T>C​(p.Val248Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,612,440 control chromosomes in the GnomAD database, including 5,448 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1791 hom., cov: 32)
  • Exomes 𝑓: 0.052 (3657 hom.)
• Consequence: CALCOCO2 NM_005831.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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]

CALCOCO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003417194).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCOCO2	NM_005831.5	c.743T>C	p.Val248Ala	missense_variant	8/13	ENST00000258947.8	NP_005822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCOCO2	ENST00000258947.8	c.743T>C	p.Val248Ala	missense_variant	8/13	1	NM_005831.5	ENSP00000258947.3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17275 AN: 152046 Hom.: 1776 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0823

GnomAD3 exomes AF: 0.0739 AC: 18567 AN: 251120 Hom.: 1266 AF XY: 0.0729 AC XY: 9897 AN XY: 135744

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.0638

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0460

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0600

Gnomad NFE exome AF: 0.0400

Gnomad OTH exome AF: 0.0566

GnomAD4 exome AF: 0.0519 AC: 75823 AN: 1460276 Hom.: 3657 Cov.: 30 AF XY: 0.0539 AC XY: 39127 AN XY: 726512

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.0643

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.0420

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0576

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0645

GnomAD4 genome AF: 0.114 AC: 17330 AN: 152164 Hom.: 1791 Cov.: 32 AF XY: 0.114 AC XY: 8504 AN XY: 74398

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0590

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.0533

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.0540 Hom.: 1114

Bravo AF: 0.118

TwinsUK AF: 0.0407 AC: 151

ALSPAC AF: 0.0379 AC: 146

ESP6500AA AF: 0.268 AC: 1183

ESP6500EA AF: 0.0377 AC: 324

ExAC AF: 0.0787 AC: 9555

Asia WGS AF: 0.135 AC: 470 AN: 3478

EpiCase AF: 0.0398

EpiControl AF: 0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0032	T;.;.;.;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.65	T;T;T;T;T;T
MetaRNN	Benign	0.0034	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M;.;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.11	T;T;T;D;T;D
Sift4G	Benign	0.81	T;T;T;T;T;T
Polyphen		0.095	B;.;.;.;.;.
Vest4		0.064
MPC		0.56
ClinPred		0.012	T
GERP RS		4.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.074
gMVP		0.059

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: rs2303015; hg19: chr17-46929908;