11-85982310-C-T

Variant names:

• chr11-85982310-C-T
• rs554750
• NM_007166.4:c.1517-307G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007166.4(PICALM):​c.1517-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 224,126 control chromosomes in the GnomAD database, including 5,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3944 hom., cov: 30)
  • Exomes 𝑓: 0.19 (1458 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.42
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-85982310-C-T is Benign according to our data. Variant chr11-85982310-C-T is described in ClinVar as Benign. ClinVar VariationId is 1230276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.1517-307G>A		intron	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.1496-307G>A		intron	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.1517-307G>A		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.1517-307G>A		intron	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.1496-307G>A		intron	N/A	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.1367-307G>A		intron	N/A	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33504 AN: 151358 Hom.: 3945 Cov.: 30

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.188 AC: 13630 AN: 72652 Hom.: 1458 AF XY: 0.188 AC XY: 7160 AN XY: 38060

African (AFR) AF: 0.316 AC: 933 AN: 2948

American (AMR) AF: 0.200 AC: 926 AN: 4640

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 468 AN: 2330

East Asian (EAS) AF: 0.112 AC: 681 AN: 6098

South Asian (SAS) AF: 0.205 AC: 1551 AN: 7566

European-Finnish (FIN) AF: 0.132 AC: 257 AN: 1950

Middle Eastern (MID) AF: 0.210 AC: 52 AN: 248

European-Non Finnish (NFE) AF: 0.187 AC: 8060 AN: 43026

Other (OTH) AF: 0.183 AC: 702 AN: 3846

GnomAD4 genome AF: 0.221 AC: 33518 AN: 151474 Hom.: 3944 Cov.: 30 AF XY: 0.217 AC XY: 16045 AN XY: 73982

African (AFR) AF: 0.304 AC: 12526 AN: 41256

American (AMR) AF: 0.204 AC: 3099 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 695 AN: 3466

East Asian (EAS) AF: 0.112 AC: 581 AN: 5168

South Asian (SAS) AF: 0.194 AC: 929 AN: 4796

European-Finnish (FIN) AF: 0.131 AC: 1360 AN: 10388

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13541 AN: 67872

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.224 Hom.: 605

Bravo AF: 0.230

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.48
PhyloP100		-2.4
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: rs554750; hg19: chr11-85693353;