rs2077815

Positions:

• chr11-85961340-G-A

Variant summary

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

The NM_007166.4(PICALM):​c.1945-2280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,224 control chromosomes in the GnomAD database, including 50,213 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 (50213 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1945-2280C>T		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1945-2280C>T		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123312 AN: 152106 Hom.: 50169 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.811 AC: 123413 AN: 152224 Hom.: 50213 Cov.: 32 AF XY: 0.807 AC XY: 60016 AN XY: 74408

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.785

Alfa AF: 0.799 Hom.: 30705

Bravo AF: 0.810

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.29

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: rs2077815; hg19: chr11-85672383;