rs10501602

chr11-85970346-A-G

Variant summary

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

The NM_007166.4(PICALM):c.1944+4362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,278 control chromosomes in the GnomAD database, including 923 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 0.10 (923 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1944+4362T>C		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1944+4362T>C		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15569 AN: 152160 Hom.: 922 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0898

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

GnomAD4 genome AF: 0.102 AC: 15575 AN: 152278 Hom.: 923 Cov.: 32 AF XY: 0.105 AC XY: 7830 AN XY: 74452

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.117 Hom.: 1479

Bravo AF: 0.0966

Asia WGS AF: 0.0980 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10501602; hg19: chr11-85681389;