11-85974531-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.1944+177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 709,054 control chromosomes in the GnomAD database, including 12,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2497 hom., cov: 32)
  • Exomes 𝑓: 0.17 (10139 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.201

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=-0.62).
• BP6: Variant 11-85974531-C-T is Benign according to our data. Variant chr11-85974531-C-T is described in ClinVar as [Benign]. Clinvar id is 1272654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICALM	NM_007166.4	c.1944+177G>A		intron_variant		ENST00000393346.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICALM	ENST00000393346.8	c.1944+177G>A		intron_variant		1	NM_007166.4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24204 AN: 152072 Hom.: 2496 Cov.: 32

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.173 AC: 96510 AN: 556862 Hom.: 10139 Cov.: 4 AF XY: 0.170 AC XY: 51732 AN XY: 305070

Gnomad4 AFR exome AF: 0.0637

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.000395

Gnomad4 SAS exome AF: 0.0749

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.159 AC: 24193 AN: 152192 Hom.: 2497 Cov.: 32 AF XY: 0.160 AC XY: 11913 AN XY: 74412

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.180

Alfa AF: 0.169 Hom.: 436

Bravo AF: 0.144

Asia WGS AF: 0.0440 AC: 155 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	14
Dann	Benign	0.61

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: rs4944550; hg19: chr11-85685574;