Variant 11-86007598-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_007166.4(PICALM):c.766-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,306,846 control chromosomes in the GnomAD database, including 28,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2836 hom., cov: 32)

Exomes 𝑓: 0.21 ( 25688 hom. )

Consequence

PICALM
NM_007166.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.142

Variant links:

Genes affected

PICALM (HGNC:15514): (phosphatidylinositol binding clathrin assembly protein) This gene encodes a clathrin assembly protein, which recruits clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. The protein may be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. The protein is involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. A chromosomal translocation t(10;11)(p13;q14) leading to the fusion of this gene and the MLLT10 gene is found in acute lymphoblastic leukemia, acute myeloid leukemia and malignant lymphomas. The polymorphisms of this gene are associated with the risk of Alzheimer disease. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

PICALM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-86007598-T-C is Benign according to our data. Variant chr11-86007598-T-C is described in ClinVar as [Benign]. Clinvar id is 403298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-86007598-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICALM	NM_007166.4 linkuse as main transcript	c.766-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8 linkuse as main transcript	c.766-15A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_007166.4	ENSP00000377015		Q13492-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27688

AN:

151990

Hom.:

2838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.240

AC:

51024

AN:

212604

Hom.:

6687

AF XY:

0.238

AC XY:

27755

AN XY:

116700

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.535

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.206

AC:

238301

AN:

1154738

Hom.:

25688

Cov.:

AF XY:

0.209

AC XY:

122010

AN XY:

583468

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.182

AC:

27693

AN:

152108

Hom.:

2836

Cov.:

AF XY:

0.181

AC XY:

13467

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.176

Hom.:

1348

Bravo

AF:

0.183

Asia WGS

AF:

0.333

AC:

1150

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Uncertain

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.75

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.75

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over