rs6950504

chr7-83075249-A-G

Variant summary

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

The NM_033026.6(PCLO):c.3300+59001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,930 control chromosomes in the GnomAD database, including 17,811 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 0.48 (17811 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCLO	NM_033026.6	c.3300+59001T>C		intron_variant		ENST00000333891.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCLO	ENST00000333891.14	c.3300+59001T>C		intron_variant		2	NM_033026.6	P1
PCLO	ENST00000423517.6	c.3300+59001T>C		intron_variant		5
PCLO	ENST00000461143.1	n.361+59001T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73242 AN: 151812 Hom.: 17794 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.482 AC: 73299 AN: 151930 Hom.: 17811 Cov.: 32 AF XY: 0.484 AC XY: 35936 AN XY: 74230

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.491

Alfa AF: 0.487 Hom.: 8548

Bravo AF: 0.479

Asia WGS AF: 0.399 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.7
Dann	Benign	0.60

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: rs6950504; hg19: chr7-82704565;