7-82766415-G-A

Position:

• chr7-82766415-G-A

Variant summary

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

The NM_033026.6(PCLO):​c.15008-4922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,692 control chromosomes in the GnomAD database, including 17,374 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 0.46 (17374 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCLO	NM_033026.6	c.15008-4922C>T		intron_variant		ENST00000333891.14
PCLO	XM_017012006.3	c.8096-4922C>T		intron_variant
PCLO	XM_047420210.1	c.15191-4922C>T		intron_variant
PCLO	XM_047420211.1	c.14717-4922C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCLO	ENST00000333891.14	c.15008-4922C>T		intron_variant		2	NM_033026.6	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69469 AN: 151574 Hom.: 17355 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.458 AC: 69520 AN: 151692 Hom.: 17374 Cov.: 31 AF XY: 0.462 AC XY: 34261 AN XY: 74086

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.466

Alfa AF: 0.483 Hom.: 2801

Bravo AF: 0.449

Asia WGS AF: 0.654 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.67

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: rs1157530; hg19: chr7-82395731;