rs2837267

chr21-39887215-C-Tchr21-39887215-C-A

Variant summary

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

The NM_006198.3(PCP4):c.10-11261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,892 control chromosomes in the GnomAD database, including 4,094 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 0.22 (4094 hom., cov: 33)
• Consequence: PCP4 NM_006198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

PCP4 (HGNC:8742): (Purkinje cell protein 4) Enables calcium ion binding activity and calmodulin binding activity. Involved in calmodulin dependent kinase signaling pathway and positive regulation of neuron differentiation. Located in cytosol and nucleus. Part of protein-containing complex. Biomarker of Huntington's disease and leiomyoma. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCP4	NM_006198.3	c.10-11261C>T		intron_variant		ENST00000328619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCP4	ENST00000328619.10	c.10-11261C>T		intron_variant		1	NM_006198.3	P1
PCP4	ENST00000462224.5	c.10-11261C>T		intron_variant, NMD_transcript_variant		2
PCP4	ENST00000468717.5	n.240+3583C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34103 AN: 151774 Hom.: 4095 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.225 AC: 34127 AN: 151892 Hom.: 4094 Cov.: 33 AF XY: 0.228 AC XY: 16889 AN XY: 74218

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.234

Alfa AF: 0.136 Hom.: 381

Bravo AF: 0.215

Asia WGS AF: 0.323 AC: 1115 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.045
Dann	Benign	0.47

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: rs2837267; hg19: chr21-41259140;