rs17148741

Positions:

• chr11-86054749-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007166.4(PICALM):​c.130+13902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,162 control chromosomes in the GnomAD database, including 512 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 0.060 (512 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICALM	NM_007166.4	c.130+13902G>A		intron_variant		ENST00000393346.8	NP_009097.2
LOC124902730	XR_007062822.1	n.9128G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.130+13902G>A		intron_variant		1	NM_007166.4	ENSP00000377015

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9163 AN: 152044 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0509

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

GnomAD4 genome AF: 0.0605 AC: 9204 AN: 152162 Hom.: 512 Cov.: 32 AF XY: 0.0573 AC XY: 4266 AN XY: 74396

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0503

Alfa AF: 0.0307 Hom.: 205

Bravo AF: 0.0660

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs17148741; hg19: chr11-85765791;