11-85983565-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007166.4(PICALM):c.1516+301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,884 control chromosomes in the GnomAD database, including 2,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2528 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-85983565-A-G is Benign according to our data. Variant chr11-85983565-A-G is described in ClinVar as [Benign]. Clinvar id is 1230620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1516+301T>C		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1516+301T>C		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24298 AN: 151766 Hom.: 2527 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.000969

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.160 AC: 24287 AN: 151884 Hom.: 2528 Cov.: 32 AF XY: 0.161 AC XY: 11943 AN XY: 74264

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.000972

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.177 Hom.: 316

Bravo AF: 0.145

Asia WGS AF: 0.0440 AC: 155 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	12
Dann	Benign	0.79
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: rs72951266; hg19: chr11-85694608;