11-85964391-C-T

Variant names:

• chr11-85964391-C-T
• rs11234495
• NM_007166.4:c.1945-5331G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007166.4(PICALM):​c.1945-5331G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,996 control chromosomes in the GnomAD database, including 4,409 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 0.24 (4409 hom., cov: 30)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4	c.1945-5331G>A		intron_variant	Intron 19 of 19	ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.1945-5331G>A		intron_variant	Intron 19 of 19	1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35895 AN: 151878 Hom.: 4398 Cov.: 30

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0859

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.236 AC: 35940 AN: 151996 Hom.: 4409 Cov.: 30 AF XY: 0.233 AC XY: 17330 AN XY: 74308

African (AFR) AF: 0.252 AC: 10428 AN: 41422

American (AMR) AF: 0.236 AC: 3603 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2422 AN: 5168

South Asian (SAS) AF: 0.243 AC: 1169 AN: 4812

European-Finnish (FIN) AF: 0.175 AC: 1850 AN: 10568

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15291 AN: 67960

Other (OTH) AF: 0.230 AC: 485 AN: 2108

Alfa AF: 0.226 Hom.: 2489

Bravo AF: 0.242

Asia WGS AF: 0.358 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.65
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11234495; hg19: chr11-85675434;