chr11-85957120-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	NM_007166.4	MANE Select	c.*1926C>T		downstream_gene	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.*1926C>T		downstream_gene	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.*1926C>T		downstream_gene	N/A	NP_001397963.1	Q13492-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000393346.8	TSL:1 MANE Select	c.*1926C>T		downstream_gene	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000890386.1		c.*1926C>T		downstream_gene	N/A	ENSP00000560445.1
	PICALM	ENST00000890388.1		c.*1926C>T		downstream_gene	N/A	ENSP00000560447.1

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

African (AFR) AF: 0.345 AC: 14127 AN: 40938

American (AMR) AF: 0.255 AC: 3860 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3464

East Asian (EAS) AF: 0.115 AC: 587 AN: 5124

South Asian (SAS) AF: 0.300 AC: 1439 AN: 4800

European-Finnish (FIN) AF: 0.177 AC: 1759 AN: 9932

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.265 AC: 17966 AN: 67706

Other (OTH) AF: 0.271 AC: 565 AN: 2086

Alfa AF: 0.271 Hom.: 7077

Bravo AF: 0.281

Asia WGS AF: 0.183 AC: 639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs622110; hg19: chr11-85668163;