rs10792821

Variant names:

• chr11-86007598-T-C
• rs10792821
• NM_007166.4:c.766-15A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-86007598-T-C
• chr11-86007598-T-A
• chr11-86007598-T-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_007166.4(PICALM):​c.766-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,306,846 control chromosomes in the GnomAD database, including 28,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2836 hom., cov: 32)
  • Exomes 𝑓: 0.21 (25688 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.142
• 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 -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 11-86007598-T-C is Benign according to our data. Variant chr11-86007598-T-C is described in ClinVar as Benign. ClinVar VariationId is 403298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 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.766-15A>G		intron	N/A	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.766-15A>G		intron	N/A	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.766-15A>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.766-15A>G		intron	N/A	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.766-15A>G		intron	N/A	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.766-15A>G		intron	N/A	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27688 AN: 151990 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.240 AC: 51024 AN: 212604 AF XY: 0.238

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.535

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.206 AC: 238301 AN: 1154738 Hom.: 25688 Cov.: 16 AF XY: 0.209 AC XY: 122010 AN XY: 583468

African (AFR) AF: 0.122 AC: 3033 AN: 24910

American (AMR) AF: 0.254 AC: 8909 AN: 35090

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4019 AN: 21928

East Asian (EAS) AF: 0.460 AC: 16491 AN: 35886

South Asian (SAS) AF: 0.269 AC: 17610 AN: 65368

European-Finnish (FIN) AF: 0.179 AC: 8681 AN: 48380

Middle Eastern (MID) AF: 0.138 AC: 633 AN: 4576

European-Non Finnish (NFE) AF: 0.194 AC: 168630 AN: 870486

Other (OTH) AF: 0.214 AC: 10295 AN: 48114

GnomAD4 genome AF: 0.182 AC: 27693 AN: 152108 Hom.: 2836 Cov.: 32 AF XY: 0.181 AC XY: 13467 AN XY: 74370

African (AFR) AF: 0.116 AC: 4829 AN: 41518

American (AMR) AF: 0.201 AC: 3071 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2422 AN: 5182

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1602 AN: 10530

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13579 AN: 67988

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.179 Hom.: 1865

Bravo AF: 0.183

Asia WGS AF: 0.333 AC: 1150 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Uncertain	23
DANN	Benign	0.50
PhyloP100		-0.14
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)		0.75		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.75		Position offset: -1

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

Other links and lift over

dbSNP: rs10792821; hg19: chr11-85718641;