NM_007166.4:c.131-14936G>A

Variant names:

• chr11-86046547-C-T
• rs677909
• NM_007166.4:c.131-14936G>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.131-14936G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 151,998 control chromosomes in the GnomAD database, including 39,488 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 0.72 (39488 hom., cov: 31)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 30 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]

LOC124902730 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	NM_007166.4	MANE Select	c.131-14936G>A		intron	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.131-14936G>A		intron	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.131-14936G>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.131-14936G>A		intron	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.131-14936G>A		intron	N/A	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.131-14936G>A		intron	N/A	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108655 AN: 151880 Hom.: 39447 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.715 AC: 108751 AN: 151998 Hom.: 39488 Cov.: 31 AF XY: 0.708 AC XY: 52563 AN XY: 74284

African (AFR) AF: 0.862 AC: 35728 AN: 41468

American (AMR) AF: 0.637 AC: 9726 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3087 AN: 5176

South Asian (SAS) AF: 0.590 AC: 2847 AN: 4822

European-Finnish (FIN) AF: 0.646 AC: 6817 AN: 10550

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.679 AC: 46155 AN: 67932

Other (OTH) AF: 0.702 AC: 1482 AN: 2110

Alfa AF: 0.686 Hom.: 19220

Bravo AF: 0.721

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.43
PhyloP100		0.28
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: rs677909; hg19: chr11-85757589;