16-12800999-T-C

Variant names:

• chr16-12800999-T-C
• rs12598821
• NM_018340.3:c.70+2708A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPPED1	NM_018340.3	c.70+2708A>G		intron_variant	Intron 1 of 3	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2	c.70+2708A>G		intron_variant	Intron 1 of 2		NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9	c.70+2708A>G		intron_variant	Intron 1 of 3	1	NM_018340.3	ENSP00000371193.4
CPPED1	ENST00000433677.6	c.70+2708A>G		intron_variant	Intron 1 of 2	1		ENSP00000411127.2
CPPED1	ENST00000261660.4	c.70+2708A>G		intron_variant	Intron 1 of 2	2		ENSP00000261660.4
CPPED1	ENST00000539677.1	n.138+2708A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.470 AC: 19469 AN: 41434

American (AMR) AF: 0.225 AC: 3434 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5176

South Asian (SAS) AF: 0.135 AC: 654 AN: 4832

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10596

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11465 AN: 67998

Other (OTH) AF: 0.234 AC: 495 AN: 2116

Alfa AF: 0.197 Hom.: 9808

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
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12598821; hg19: chr16-12894856;