11-86069540-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_001206947.2	c.-24+180C>A		intron_variant	Intron 1 of 18		NP_001193876.1
PICALM	XM_047427660.1	c.-24+180C>A		intron_variant	Intron 1 of 21		XP_047283616.1
PICALM	XM_047427666.1	c.-24+180C>A		intron_variant	Intron 1 of 18		XP_047283622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000528398.5	c.-24+180C>A		intron_variant	Intron 1 of 18	2		ENSP00000434884.1
PICALM	ENST00000531930.5	c.-56+180C>A		intron_variant	Intron 1 of 6	5		ENSP00000433303.1
PICALM	ENST00000525162.5	c.-106C>A		upstream_gene_variant		4		ENSP00000436508.1
PICALM	ENST00000528411.1	n.-229C>A		upstream_gene_variant		5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0808 Hom.: 137

Bravo AF: 0.116

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10898433; hg19: chr11-85780582;