chr11-85966428-A-G

Variant names:

• chr11-85966428-A-G
• rs17817600
• NM_007166.4:c.1945-7368T>C

Variant summary

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

The NM_007166.4(PICALM):​c.1945-7368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,222 control chromosomes in the GnomAD database, including 929 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 0.099 (929 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	NM_007166.4	MANE Select	c.1945-7368T>C		intron	N/A	NP_009097.2
	PICALM	NM_001206946.2		c.1924-7368T>C		intron	N/A	NP_001193875.1
	PICALM	NM_001411034.1		c.1885-7368T>C		intron	N/A	NP_001397963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000393346.8	TSL:1 MANE Select	c.1945-7368T>C		intron	N/A	ENSP00000377015.3
	PICALM	ENST00000526033.5	TSL:1	c.1924-7368T>C		intron	N/A	ENSP00000433846.1
	PICALM	ENST00000532317.5	TSL:1	c.1819-7368T>C		intron	N/A	ENSP00000436958.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15011 AN: 152104 Hom.: 928 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0987 AC: 15017 AN: 152222 Hom.: 929 Cov.: 32 AF XY: 0.102 AC XY: 7562 AN XY: 74402

African (AFR) AF: 0.0233 AC: 969 AN: 41570

American (AMR) AF: 0.144 AC: 2195 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 318 AN: 3468

East Asian (EAS) AF: 0.0764 AC: 395 AN: 5172

South Asian (SAS) AF: 0.131 AC: 632 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8509 AN: 68006

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.119 Hom.: 3255

Bravo AF: 0.0920

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		0.79
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: rs17817600; hg19: chr11-85677471;