chr21-39888016-A-G

Variant names:

• chr21-39888016-A-G
• rs2837269
• NM_006198.3:c.10-10460A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006198.3(PCP4):​c.10-10460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,024 control chromosomes in the GnomAD database, including 12,547 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 0.40 (12547 hom., cov: 32)
• Consequence: PCP4 NM_006198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCP4	NM_006198.3	c.10-10460A>G		intron_variant	Intron 1 of 2	ENST00000328619.10	NP_006189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCP4	ENST00000328619.10	c.10-10460A>G		intron_variant	Intron 1 of 2	1	NM_006198.3	ENSP00000329403.5
PCP4	ENST00000462224.5	n.10-10460A>G		intron_variant	Intron 1 of 3	2		ENSP00000433172.1
PCP4	ENST00000468717.5	n.240+4384A>G		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60041 AN: 151906 Hom.: 12532 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.395 AC: 60095 AN: 152024 Hom.: 12547 Cov.: 32 AF XY: 0.402 AC XY: 29879 AN XY: 74312

African (AFR) AF: 0.433 AC: 17953 AN: 41438

American (AMR) AF: 0.379 AC: 5799 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3902 AN: 5168

South Asian (SAS) AF: 0.589 AC: 2840 AN: 4824

European-Finnish (FIN) AF: 0.391 AC: 4125 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22680 AN: 67968

Other (OTH) AF: 0.391 AC: 823 AN: 2104

Alfa AF: 0.357 Hom.: 18252

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.56
PhyloP100		0.94
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: rs2837269; hg19: chr21-41259941;