11-85982310-C-T

Position:

• chr11-85982310-C-T

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.1517-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 224,126 control chromosomes in the GnomAD database, including 5,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3944 hom., cov: 30)
  • Exomes 𝑓: 0.19 (1458 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.42

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=-0.91).
• BP6: Variant 11-85982310-C-T is Benign according to our data. Variant chr11-85982310-C-T is described in ClinVar as [Benign]. Clinvar id is 1230276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1517-307G>A		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1517-307G>A		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33504 AN: 151358 Hom.: 3945 Cov.: 30

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.188 AC: 13630 AN: 72652 Hom.: 1458 AF XY: 0.188 AC XY: 7160 AN XY: 38060

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.221 AC: 33518 AN: 151474 Hom.: 3944 Cov.: 30 AF XY: 0.217 AC XY: 16045 AN XY: 73982

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.211

Alfa AF: 0.221 Hom.: 574

Bravo AF: 0.230

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.48

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: rs554750; hg19: chr11-85693353;