11-85980619-G-C

Position:

• chr11-85980619-G-C

Variant summary

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

The NM_007166.4(PICALM):​c.1779+510C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,130 control chromosomes in the GnomAD database, including 50,009 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 0.81 (50009 hom., cov: 31)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICALM	NM_007166.4	c.1779+510C>G		intron_variant		ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.1779+510C>G		intron_variant		1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123067 AN: 152012 Hom.: 49965 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.810 AC: 123168 AN: 152130 Hom.: 50009 Cov.: 31 AF XY: 0.806 AC XY: 59929 AN XY: 74372

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.782

Alfa AF: 0.815 Hom.: 5180

Bravo AF: 0.807

Asia WGS AF: 0.701 AC: 2437 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.70

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: rs588076; hg19: chr11-85691662;