11-85981299-A-C

Variant names:

• chr11-85981299-A-C
• rs2508688
• NM_007166.4:c.1680-71T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007166.4(PICALM):​c.1680-71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 906,354 control chromosomes in the GnomAD database, including 286,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50565 hom., cov: 32)
  • Exomes 𝑓: 0.79 (235883 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.770
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-85981299-A-C is Benign according to our data. Variant chr11-85981299-A-C is described in ClinVar as Benign. ClinVar VariationId is 1174406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 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.1680-71T>G		intron	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.1659-71T>G		intron	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.1680-71T>G		intron	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.1680-71T>G		intron	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.1659-71T>G		intron	N/A	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.1530-71T>G		intron	N/A	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123715 AN: 152054 Hom.: 50521 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.789 AC: 595371 AN: 754182 Hom.: 235883 AF XY: 0.788 AC XY: 315353 AN XY: 400406

African (AFR) AF: 0.887 AC: 16207 AN: 18276

American (AMR) AF: 0.752 AC: 28985 AN: 38546

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 15172 AN: 20556

East Asian (EAS) AF: 0.685 AC: 23336 AN: 34060

South Asian (SAS) AF: 0.737 AC: 49217 AN: 66746

European-Finnish (FIN) AF: 0.809 AC: 38858 AN: 48050

Middle Eastern (MID) AF: 0.759 AC: 3210 AN: 4228

European-Non Finnish (NFE) AF: 0.804 AC: 391588 AN: 487172

Other (OTH) AF: 0.788 AC: 28798 AN: 36548

GnomAD4 genome AF: 0.814 AC: 123816 AN: 152172 Hom.: 50565 Cov.: 32 AF XY: 0.809 AC XY: 60213 AN XY: 74394

African (AFR) AF: 0.882 AC: 36625 AN: 41528

American (AMR) AF: 0.778 AC: 11895 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3494 AN: 5178

South Asian (SAS) AF: 0.736 AC: 3550 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8568 AN: 10570

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54616 AN: 68002

Other (OTH) AF: 0.787 AC: 1663 AN: 2112

Alfa AF: 0.786 Hom.: 2676

Bravo AF: 0.812

Asia WGS AF: 0.702 AC: 2445 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.14
PhyloP100		0.77
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: rs2508688; hg19: chr11-85692342;