chr11-86069540-G-T

Variant names:

• chr11-86069540-G-T
• rs10898433
• NM_001206947.2:c.-24+180C>A

Variant summary

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

The NM_001206947.2(PICALM):​c.-24+180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,352 control chromosomes in the GnomAD database, including 1,449 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 0.12 (1448 hom., cov: 32)
  • Exomes 𝑓: 0.096 (1 hom.)
• Consequence: PICALM NM_001206947.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 6 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]

ENSG00000309910 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206947.2. 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_001206947.2		c.-24+180C>A		intron	N/A	NP_001193876.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000528398.5	TSL:2	c.-24+180C>A		intron	N/A	ENSP00000434884.1
	PICALM	ENST00000531930.5	TSL:5	c.-56+180C>A		intron	N/A	ENSP00000433303.1
	ENSG00000309910	ENST00000845444.1		n.180+207G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18096 AN: 152100 Hom.: 1448 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0956 AC: 13 AN: 136 Hom.: 1 Cov.: 0 AF XY: 0.0932 AC XY: 11 AN XY: 118

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.125 AC: 5 AN: 40

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0814 AC: 7 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.119 AC: 18099 AN: 152216 Hom.: 1448 Cov.: 32 AF XY: 0.120 AC XY: 8919 AN XY: 74414

African (AFR) AF: 0.0356 AC: 1480 AN: 41554

American (AMR) AF: 0.147 AC: 2254 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1887 AN: 5146

South Asian (SAS) AF: 0.183 AC: 884 AN: 4820

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9676 AN: 67996

Other (OTH) AF: 0.107 AC: 226 AN: 2114

Alfa AF: 0.0788 Hom.: 137

Bravo AF: 0.116

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.49
PhyloP100		-0.66
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10898433; hg19: chr11-85780582;