11-86063520-T-G

Position:

• chr11-86063520-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007166.4(PICALM):​c.130+5131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,032 control chromosomes in the GnomAD database, including 14,735 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 0.44 (14735 hom., cov: 33)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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]

LOC124902730 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICALM	NM_007166.4	c.130+5131A>C		intron_variant		ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.130+5131A>C		intron_variant		1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66462 AN: 151914 Hom.: 14735 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.437 AC: 66487 AN: 152032 Hom.: 14735 Cov.: 33 AF XY: 0.432 AC XY: 32135 AN XY: 74328

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.438

Alfa AF: 0.448 Hom.: 1873

Bravo AF: 0.446

Asia WGS AF: 0.515 AC: 1790 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.50

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: rs3016786; hg19: chr11-85774562;