Variant 11-85974531-C-T 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.1944+177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 709,054 control chromosomes in the GnomAD database, including 12,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2497 hom., cov: 32)

Exomes 𝑓: 0.17 ( 10139 hom. )

Consequence

PICALM
NM_007166.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-85974531-C-T is Benign according to our data. Variant chr11-85974531-C-T is described in ClinVar as [Benign]. Clinvar id is 1272654.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.1944+177G>A		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8 linkuse as main transcript	c.1944+177G>A		intron_variant		1	NM_007166.4		Q13492-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24204

AN:

152072

Hom.:

2496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.173

AC:

96510

AN:

556862

Hom.:

10139

Cov.:

AF XY:

0.170

AC XY:

51732

AN XY:

305070

show subpopulations

Gnomad4 AFR exome

AF:

0.0637

Gnomad4 AMR exome

AF:

0.0962

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.000395

Gnomad4 SAS exome

AF:

0.0749

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.159

AC:

24193

AN:

152192

Hom.:

2497

Cov.:

AF XY:

0.160

AC XY:

11913

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0649

Gnomad4 FIN

AF:

0.313

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.169

Hom.:

436

Bravo

AF:

0.144

Asia WGS

AF:

0.0440

AC:

155

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

-0.62

CADD

Benign

DANN

Benign

0.61

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