Variant chr11-85981018-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007166.4(PICALM):c.1779+111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 631,468 control chromosomes in the GnomAD database, including 12,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2495 hom., cov: 33)

Exomes 𝑓: 0.19 ( 9828 hom. )

Consequence

PICALM
NM_007166.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-85981018-A-G is Benign according to our data. Variant chr11-85981018-A-G is described in ClinVar as [Benign]. Clinvar id is 1233368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4 linkuse as main transcript	c.1779+111T>C		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8 linkuse as main transcript	c.1779+111T>C		intron_variant		1	NM_007166.4		Q13492-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24196

AN:

152144

Hom.:

2494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0665

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.186

AC:

89324

AN:

479206

Hom.:

9828

AF XY:

0.182

AC XY:

46654

AN XY:

256388

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.000394

Gnomad4 SAS exome

AF:

0.0788

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.159

AC:

24185

AN:

152262

Hom.:

2495

Cov.:

AF XY:

0.160

AC XY:

11910

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0676

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0659

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.174

Hom.:

302

Bravo

AF:

0.144

Asia WGS

AF:

0.0450

AC:

156

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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