rs10792820

Positions:

• chr11-85992931-A-C

Variant summary

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

The ENST00000393346.8(PICALM):​c.1259-2532T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,146 control chromosomes in the GnomAD database, including 3,812 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 0.21 (3812 hom., cov: 32)
• Consequence: PICALM ENST00000393346.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICALM	NM_007166.4	c.1259-2532T>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.1259-2532T>G		intron_variant		1	NM_007166.4	ENSP00000377015

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32053 AN: 152028 Hom.: 3811 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.211 AC: 32064 AN: 152146 Hom.: 3812 Cov.: 32 AF XY: 0.210 AC XY: 15617 AN XY: 74378

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.218

Alfa AF: 0.241 Hom.: 8589

Bravo AF: 0.209

Asia WGS AF: 0.360 AC: 1248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.51

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: rs10792820; hg19: chr11-85703974;