16-12800999-T-C

Position:

• chr16-12800999-T-C

Variant summary

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

The NM_018340.3(CPPED1):​c.70+2708A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,100 control chromosomes in the GnomAD database, including 6,538 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 0.26 (6538 hom., cov: 32)
• Consequence: CPPED1 NM_018340.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

CPPED1 (HGNC:25632): (calcineurin like phosphoesterase domain containing 1) Predicted to enable metal ion binding activity; protein serine phosphatase activity; and protein threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytosol and plasma membrane. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPPED1	NM_018340.3	c.70+2708A>G		intron_variant		ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2	c.70+2708A>G		intron_variant			NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9	c.70+2708A>G		intron_variant		1	NM_018340.3	ENSP00000371193	P1
CPPED1	ENST00000433677.6	c.70+2708A>G		intron_variant		1		ENSP00000411127
CPPED1	ENST00000261660.4	c.70+2708A>G		intron_variant		2		ENSP00000261660
CPPED1	ENST00000539677.1	n.138+2708A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39299 AN: 151982 Hom.: 6517 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39375 AN: 152100 Hom.: 6538 Cov.: 32 AF XY: 0.256 AC XY: 19048 AN XY: 74356

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.234

Alfa AF: 0.172 Hom.: 4209

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.58

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: rs12598821; hg19: chr16-12894856;