7-82849099-T-G

Position:

• chr7-82849099-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033026.6(PCLO):​c.13655-1852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,932 control chromosomes in the GnomAD database, including 12,621 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 0.39 (12621 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCLO	NM_033026.6	c.13655-1852A>C		intron_variant		ENST00000333891.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCLO	ENST00000333891.14	c.13655-1852A>C		intron_variant		2	NM_033026.6	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58962 AN: 151814 Hom.: 12605 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.388 AC: 59010 AN: 151932 Hom.: 12621 Cov.: 32 AF XY: 0.396 AC XY: 29385 AN XY: 74248

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.398

Alfa AF: 0.403 Hom.: 2613

Bravo AF: 0.376

Asia WGS AF: 0.621 AC: 2149 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.83

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: rs2522840; hg19: chr7-82478415;