7-82987519-C-G

Position:

• chr7-82987519-C-G

Variant summary

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

The NM_033026.6(PCLO):​c.3301-21032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,738 control chromosomes in the GnomAD database, including 19,531 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 0.50 (19531 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6	c.3301-21032G>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.3301-21032G>C		intron_variant		2	NM_033026.6	ENSP00000334319	P1
PCLO	ENST00000423517.6	c.3301-21032G>C		intron_variant		5		ENSP00000388393
PCLO	ENST00000461143.1	n.362-21032G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75896 AN: 151620 Hom.: 19500 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.501 AC: 75965 AN: 151738 Hom.: 19531 Cov.: 31 AF XY: 0.503 AC XY: 37274 AN XY: 74134

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.526

Alfa AF: 0.491 Hom.: 2302

Bravo AF: 0.507

Asia WGS AF: 0.678 AC: 2347 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.36

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: rs7778238; hg19: chr7-82616835;