11-85993023-T-C

Variant names:

• chr11-85993023-T-C
• rs12795381
• NM_007166.4:c.1259-2624A>G

Variant summary

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

The ENST00000393346.8(PICALM):​c.1259-2624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 151,738 control chromosomes in the GnomAD database, including 909 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 (909 hom., cov: 31)
• Consequence: PICALM ENST00000393346.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393346.8. 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.1259-2624A>G		intron	N/A	NP_009097.2
	PICALM	NM_001206946.2		c.1259-2645A>G		intron	N/A	NP_001193875.1
	PICALM	NM_001411034.1		c.1259-2624A>G		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.1259-2624A>G		intron	N/A	ENSP00000377015.3
	PICALM	ENST00000526033.5	TSL:1	c.1259-2645A>G		intron	N/A	ENSP00000433846.1
	PICALM	ENST00000532317.5	TSL:1	c.1258+3803A>G		intron	N/A	ENSP00000436958.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15051 AN: 151656 Hom.: 908 Cov.: 31

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0762

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.0992 AC: 15059 AN: 151738 Hom.: 909 Cov.: 31 AF XY: 0.102 AC XY: 7576 AN XY: 74086

African (AFR) AF: 0.0308 AC: 1273 AN: 41398

American (AMR) AF: 0.147 AC: 2234 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3468

East Asian (EAS) AF: 0.0762 AC: 395 AN: 5182

South Asian (SAS) AF: 0.131 AC: 633 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1692 AN: 10370

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.121 AC: 8245 AN: 67954

Other (OTH) AF: 0.0894 AC: 188 AN: 2102

Alfa AF: 0.103 Hom.: 121

Bravo AF: 0.0931

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		0.40
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: rs12795381; hg19: chr11-85704066;