rs676733

chr11-86022967-C-T

Variant summary

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

The NM_007166.4(PICALM):c.350-498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,970 control chromosomes in the GnomAD database, including 38,864 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 0.71 (38864 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.350-498G>A		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.350-498G>A		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107916 AN: 151852 Hom.: 38824 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.711 AC: 108012 AN: 151970 Hom.: 38864 Cov.: 32 AF XY: 0.703 AC XY: 52237 AN XY: 74260

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.699

Alfa AF: 0.711 Hom.: 5669

Bravo AF: 0.716

Asia WGS AF: 0.602 AC: 2077 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.70
Dann	Benign	0.48

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: rs676733; hg19: chr11-85734010;