rs2715148

Variant names:

• chr7-82820719-A-C
• rs2715148
• NM_033026.6:c.14791+1776T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-82820719-A-C
• chr7-82820719-A-G
• chr7-82820719-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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]

PCLO Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.14791+1776T>G		intron_variant	Intron 20 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.14791+1776T>G		intron_variant	Intron 20 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000423517.6	c.*1759T>G		3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000388393.2
PCLO	ENST00000432078.2	n.279+393T>G		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.702 AC: 16095 AN: 22938

American (AMR) AF: 0.571 AC: 4807 AN: 8412

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 6613 AN: 14370

East Asian (EAS) AF: 0.876 AC: 23196 AN: 26476

South Asian (SAS) AF: 0.615 AC: 11970 AN: 19464

European-Finnish (FIN) AF: 0.501 AC: 10560 AN: 21094

Middle Eastern (MID) AF: 0.524 AC: 1525 AN: 2910

European-Non Finnish (NFE) AF: 0.497 AC: 456423 AN: 918664

Other (OTH) AF: 0.530 AC: 23128 AN: 43598

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

African (AFR) AF: 0.691 AC: 28635 AN: 41464

American (AMR) AF: 0.558 AC: 8515 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4390 AN: 5168

South Asian (SAS) AF: 0.622 AC: 2997 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5191 AN: 10572

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33499 AN: 67952

Other (OTH) AF: 0.560 AC: 1179 AN: 2106

Alfa AF: 0.528 Hom.: 51069

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2715148; hg19: chr7-82450035;