11-85970346-A-G

Variant names:

• chr11-85970346-A-G
• rs10501602
• NM_007166.4:c.1944+4362T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007166.4(PICALM):​c.1944+4362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,278 control chromosomes in the GnomAD database, including 923 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 0.10 (923 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 14 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	NM_007166.4	MANE Select	c.1944+4362T>C		intron	N/A	NP_009097.2
	PICALM	NM_001206946.2		c.1923+4362T>C		intron	N/A	NP_001193875.1
	PICALM	NM_001411034.1		c.1884+4362T>C		intron	N/A	NP_001397963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000393346.8	TSL:1 MANE Select	c.1944+4362T>C		intron	N/A	ENSP00000377015.3
	PICALM	ENST00000526033.5	TSL:1	c.1923+4362T>C		intron	N/A	ENSP00000433846.1
	PICALM	ENST00000532317.5	TSL:1	c.1818+4362T>C		intron	N/A	ENSP00000436958.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15569 AN: 152160 Hom.: 922 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0898

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

GnomAD4 genome AF: 0.102 AC: 15575 AN: 152278 Hom.: 923 Cov.: 32 AF XY: 0.105 AC XY: 7830 AN XY: 74452

African (AFR) AF: 0.0423 AC: 1759 AN: 41572

American (AMR) AF: 0.146 AC: 2231 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3468

East Asian (EAS) AF: 0.0773 AC: 401 AN: 5190

South Asian (SAS) AF: 0.137 AC: 661 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1704 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8233 AN: 68016

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.115 Hom.: 1832

Bravo AF: 0.0966

Asia WGS AF: 0.0980 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10501602; hg19: chr11-85681389;