7-82926353-A-T

Position:

• chr7-82926353-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.11113-9480T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,928 control chromosomes in the GnomAD database, including 28,176 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 0.60 (28176 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6	c.11113-9480T>A		intron_variant		ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.11113-9480T>A		intron_variant		2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000437081.1	c.1273-9480T>A		intron_variant		1		ENSP00000393760.1
PCLO	ENST00000423517.6	c.11113-9480T>A		intron_variant		5		ENSP00000388393.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90718 AN: 151810 Hom.: 28112 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.598 AC: 90848 AN: 151928 Hom.: 28176 Cov.: 32 AF XY: 0.598 AC XY: 44366 AN XY: 74228

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.586

Alfa AF: 0.552 Hom.: 2979

Bravo AF: 0.611

Asia WGS AF: 0.727 AC: 2511 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.28

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: rs2107828; hg19: chr7-82555669;