rs2715148

chr7-82820719-A-Cchr7-82820719-A-Gchr7-82820719-A-T

Variant summary

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

The NM_033026.6(PCLO):c.14791+1776T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,229,950 control chromosomes in the GnomAD database, including 171,114 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 0.57 (25708 hom., cov: 33)
  • Exomes 𝑓: 0.51 (145406 hom.)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCLO	NM_033026.6	c.14791+1776T>G		intron_variant		ENST00000333891.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCLO	ENST00000333891.14	c.14791+1776T>G		intron_variant		2	NM_033026.6	P1
PCLO	ENST00000423517.6	c.*1759T>G		3_prime_UTR_variant	20/20	5
PCLO	ENST00000432078.2	n.279+393T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86488 AN: 151906 Hom.: 25647 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.514 AC: 554317 AN: 1077926 Hom.: 145406 Cov.: 31 AF XY: 0.513 AC XY: 261267 AN XY: 508848

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.570 AC: 86620 AN: 152024 Hom.: 25708 Cov.: 33 AF XY: 0.570 AC XY: 42358 AN XY: 74284

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.560

Alfa AF: 0.514 Hom.: 29375

Bravo AF: 0.581

Asia WGS AF: 0.740 AC: 2570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	18
Dann	Benign	0.81

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: rs2715148; hg19: chr7-82450035;