11-85978392-T-C

Position:

• chr11-85978392-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007166.4(PICALM):​c.1780-1710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 197,218 control chromosomes in the GnomAD database, including 64,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50524 hom., cov: 31)
  • Exomes 𝑓: 0.79 (14222 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-85978392-T-C is Benign according to our data. Variant chr11-85978392-T-C is described in ClinVar as [Benign]. Clinvar id is 1252751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1780-1710A>G		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1780-1710A>G		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123626 AN: 151950 Hom.: 50480 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.791 AC: 35703 AN: 45150 Hom.: 14222 Cov.: 2 AF XY: 0.788 AC XY: 18299 AN XY: 23218

Gnomad4 AFR exome AF: 0.898

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.806

Gnomad4 OTH exome AF: 0.801

GnomAD4 genome AF: 0.814 AC: 123727 AN: 152068 Hom.: 50524 Cov.: 31 AF XY: 0.809 AC XY: 60159 AN XY: 74344

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.786

Alfa AF: 0.816 Hom.: 5918

Bravo AF: 0.812

Asia WGS AF: 0.703 AC: 2442 AN: 3468

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	-0.93
CADD	Benign	1.1
DANN	Benign	0.54

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: rs618629; hg19: chr11-85689435;