12-53716143-C-T

Position:

• chr12-53716143-C-T

Variant summary

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

The NM_020898.3(CALCOCO1):​c.1006-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,579,508 control chromosomes in the GnomAD database, including 19,833 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 0.15 (1923 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17910 hom.)
• Consequence: CALCOCO1 NM_020898.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

CALCOCO1 (HGNC:29306): (calcium binding and coiled-coil domain 1) Enables several functions, including armadillo repeat domain binding activity; beta-catenin binding activity; and nuclear receptor coactivator activity. Involved in positive regulation of gene expression and positive regulation of transcription, DNA-templated. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCOCO1	NM_020898.3	c.1006-96G>A		intron_variant		ENST00000550804.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCOCO1	ENST00000550804.6	c.1006-96G>A		intron_variant		1	NM_020898.3	P4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23487 AN: 152040 Hom.: 1925 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.151 AC: 215140 AN: 1427348 Hom.: 17910 Cov.: 28 AF XY: 0.153 AC XY: 108552 AN XY: 708578

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.154 AC: 23490 AN: 152160 Hom.: 1923 Cov.: 32 AF XY: 0.160 AC XY: 11923 AN XY: 74368

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.177

Alfa AF: 0.153 Hom.: 370

Bravo AF: 0.146

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.64

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: rs2277370; hg19: chr12-54109927; COSMIC: COSV50412409; COSMIC: COSV50412409;