rs676733

Variant names:

• chr11-86022967-C-T
• rs676733
• NM_007166.4:c.350-498G>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.350-498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,970 control chromosomes in the GnomAD database, including 38,864 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 0.71 (38864 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4	c.350-498G>A		intron_variant	Intron 3 of 19	ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.350-498G>A		intron_variant	Intron 3 of 19	1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107916 AN: 151852 Hom.: 38824 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.711 AC: 108012 AN: 151970 Hom.: 38864 Cov.: 32 AF XY: 0.703 AC XY: 52237 AN XY: 74260

African (AFR) AF: 0.845 AC: 35042 AN: 41490

American (AMR) AF: 0.634 AC: 9674 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3098 AN: 5184

South Asian (SAS) AF: 0.592 AC: 2854 AN: 4824

European-Finnish (FIN) AF: 0.647 AC: 6809 AN: 10522

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

European-Non Finnish (NFE) AF: 0.680 AC: 46150 AN: 67908

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.711 Hom.: 5669

Bravo AF: 0.716

Asia WGS AF: 0.602 AC: 2077 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.48
PhyloP100		-0.46
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: rs676733; hg19: chr11-85734010;