11-85957120-G-A

Variant names:

• chr11-85957120-G-A
• rs622110
• NM_007166.4:c.*1926C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007166.4(PICALM):​c.*1926C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 150,382 control chromosomes in the GnomAD database, including 5,938 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 0.28 (5938 hom., cov: 31)
• Consequence: PICALM NM_007166.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4	c.*1926C>T		downstream_gene_variant		ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.*1926C>T		downstream_gene_variant		1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41540 AN: 150282 Hom.: 5935 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.276 AC: 41565 AN: 150382 Hom.: 5938 Cov.: 31 AF XY: 0.273 AC XY: 20012 AN XY: 73412

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.271

Alfa AF: 0.282 Hom.: 591

Bravo AF: 0.281

Asia WGS AF: 0.183 AC: 639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs622110; hg19: chr11-85668163;