rs7781142

Variant names:

• chr7-82933795-A-G
• rs7781142
• NM_033026.6:c.11112+15681T>C

Variant summary

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

The NM_033026.6(PCLO):​c.11112+15681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,794 control chromosomes in the GnomAD database, including 23,410 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 0.55 (23410 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.11112+15681T>C		intron_variant	Intron 6 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.11112+15681T>C		intron_variant	Intron 6 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000437081.1	c.1272+15681T>C		intron_variant	Intron 1 of 1	1		ENSP00000393760.1
PCLO	ENST00000423517.6	c.11112+15681T>C		intron_variant	Intron 6 of 19	5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83386 AN: 151676 Hom.: 23369 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.550 AC: 83482 AN: 151794 Hom.: 23410 Cov.: 32 AF XY: 0.551 AC XY: 40899 AN XY: 74214

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.551

Alfa AF: 0.523 Hom.: 19984

Bravo AF: 0.556

Asia WGS AF: 0.703 AC: 2440 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.41

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: rs7781142; hg19: chr7-82563111;