chr7-83150474-A-G

Position:

• chr7-83150474-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.1893+4274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,286 control chromosomes in the GnomAD database, including 579 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 0.059 (579 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6	c.1893+4274T>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.1893+4274T>C		intron_variant		2	NM_033026.6	ENSP00000334319	P1
PCLO	ENST00000423517.6	c.1893+4274T>C		intron_variant		5		ENSP00000388393

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8928 AN: 152168 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0587 AC: 8940 AN: 152286 Hom.: 579 Cov.: 32 AF XY: 0.0612 AC XY: 4557 AN XY: 74454

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0647 Hom.: 100

Bravo AF: 0.0689

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.57

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: rs4644166; hg19: chr7-82779790;