rs12707524

Positions:

• chr7-82857299-A-G

Variant summary

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

The NM_033026.6(PCLO):​c.13655-10052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,066 control chromosomes in the GnomAD database, including 2,736 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 0.18 (2736 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856

Genes affected

PCLO (HGNC:13406): (piccolo presynaptic cytomatrix protein) The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6	c.13655-10052T>C		intron_variant		ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.13655-10052T>C		intron_variant		2	NM_033026.6	ENSP00000334319	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27289 AN: 151948 Hom.: 2734 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.180 AC: 27315 AN: 152066 Hom.: 2736 Cov.: 32 AF XY: 0.182 AC XY: 13538 AN XY: 74326

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.175

Alfa AF: 0.199 Hom.: 4038

Bravo AF: 0.171

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.72

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: rs12707524; hg19: chr7-82486615;