12-53710248-G-A

Position:

• chr12-53710248-G-A

Variant summary

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

The NM_020898.3(CALCOCO1):​c.*1696C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,006 control chromosomes in the GnomAD database, including 24,463 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 0.57 (24450 hom., cov: 31)
  • Exomes 𝑓: 0.58 (13 hom.)
• Consequence: CALCOCO1 NM_020898.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCOCO1	NM_020898.3	c.*1696C>T		3_prime_UTR_variant	15/15	ENST00000550804.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCOCO1	ENST00000550804.6	c.*1696C>T		3_prime_UTR_variant	15/15	1	NM_020898.3	P4
CALCOCO1	ENST00000262059.8	c.*1696C>T		3_prime_UTR_variant	15/15	2		A1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85808 AN: 151810 Hom.: 24414 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.538

GnomAD4 exome AF: 0.577 AC: 45 AN: 78 Hom.: 13 Cov.: 0 AF XY: 0.571 AC XY: 24 AN XY: 42

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.565 AC: 85892 AN: 151928 Hom.: 24450 Cov.: 31 AF XY: 0.563 AC XY: 41777 AN XY: 74248

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.539

Alfa AF: 0.555 Hom.: 30040

Bravo AF: 0.565

Asia WGS AF: 0.515 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12309211; hg19: chr12-54104032;