11-85981299-A-T

Variant names:

• chr11-85981299-A-T
• rs2508688
• NM_007166.4:c.1680-71T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007166.4(PICALM):​c.1680-71T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 755,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	NM_007166.4	MANE Select	c.1680-71T>A		intron	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.1659-71T>A		intron	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.1680-71T>A		intron	N/A	NP_001397963.1	Q13492-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000393346.8	TSL:1 MANE Select	c.1680-71T>A		intron	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.1659-71T>A		intron	N/A	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.1530-71T>A		intron	N/A	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000794 AC: 6 AN: 755574 Hom.: 0 AF XY: 0.0000150 AC XY: 6 AN XY: 401138

African (AFR) AF: 0.00 AC: 0 AN: 18290

American (AMR) AF: 0.0000259 AC: 1 AN: 38626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20596

East Asian (EAS) AF: 0.00 AC: 0 AN: 34136

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 488092

Other (OTH) AF: 0.000109 AC: 4 AN: 36630

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.5
DANN	Benign	0.28
PhyloP100		0.77

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: rs2508688; hg19: chr11-85692342;