chr11-85959342-CAA-C

Position:

• chr11-85959342-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007166.4(PICALM):​c.1945-284_1945-283del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (37649 hom., cov: 0)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-85959342-CAA-C is Benign according to our data. Variant chr11-85959342-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1225301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1945-284_1945-283del		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1945-284_1945-283del		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106264 AN: 151510 Hom.: 37613 Cov.: 0

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.701 AC: 106355 AN: 151628 Hom.: 37649 Cov.: 0 AF XY: 0.694 AC XY: 51399 AN XY: 74036

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.692

Alfa AF: 0.698 Hom.: 4538

Bravo AF: 0.705

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs68172244; hg19: chr11-85670385;