11-85975053-T-G

Variant names:

• chr11-85975053-T-G
• rs532470
• NM_007166.4:c.1840-241A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007166.4(PICALM):​c.1840-241A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,982 control chromosomes in the GnomAD database, including 15,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (15205 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.153

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-85975053-T-G is Benign according to our data. Variant chr11-85975053-T-G is described in ClinVar as [Benign]. Clinvar id is 1261860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4	c.1840-241A>C		intron_variant	Intron 18 of 19	ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.1840-241A>C		intron_variant	Intron 18 of 19	1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67487 AN: 151864 Hom.: 15202 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.444 AC: 67518 AN: 151982 Hom.: 15205 Cov.: 32 AF XY: 0.439 AC XY: 32628 AN XY: 74284

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.439

Alfa AF: 0.376 Hom.: 1856

Bravo AF: 0.454

Asia WGS AF: 0.511 AC: 1777 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.83

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: rs532470; hg19: chr11-85686096;