11-86048986-T-C

Position:

• chr11-86048986-T-C

Variant summary

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

The NM_007166.4(PICALM):​c.131-17375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,962 control chromosomes in the GnomAD database, including 39,263 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 (39263 hom., cov: 31)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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]

LOC124902730 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.131-17375A>G		intron_variant		ENST00000393346.8
LOC124902730	XR_007062822.1	n.14891A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.131-17375A>G		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108442 AN: 151846 Hom.: 39223 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.714 AC: 108536 AN: 151962 Hom.: 39263 Cov.: 31 AF XY: 0.707 AC XY: 52466 AN XY: 74258

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.702

Alfa AF: 0.672 Hom.: 35187

Bravo AF: 0.719

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.44

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: rs694011; hg19: chr11-85760028;