rs10792821

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007166.4(PICALM):​c.766-15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,312,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.766-15A>T		intron	N/A	NP_009097.2
	PICALM	NM_001206946.2		c.766-15A>T		intron	N/A	NP_001193875.1
	PICALM	NM_001411034.1		c.766-15A>T		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.766-15A>T		intron	N/A	ENSP00000377015.3
	PICALM	ENST00000526033.5	TSL:1	c.766-15A>T		intron	N/A	ENSP00000433846.1
	PICALM	ENST00000532317.5	TSL:1	c.766-15A>T		intron	N/A	ENSP00000436958.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000273 AC: 58 AN: 212604 AF XY: 0.000163

Gnomad AFR exome AF: 0.00430

Gnomad AMR exome AF: 0.000155

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000209

GnomAD4 exome AF: 0.000122 AC: 142 AN: 1160854 Hom.: 0 Cov.: 16 AF XY: 0.0000938 AC XY: 55 AN XY: 586190

African (AFR) AF: 0.00489 AC: 122 AN: 24964

American (AMR) AF: 0.000142 AC: 5 AN: 35114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35944

South Asian (SAS) AF: 0.00 AC: 0 AN: 65494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4582

European-Non Finnish (NFE) AF: 0.00000913 AC: 8 AN: 876014

Other (OTH) AF: 0.000145 AC: 7 AN: 48366

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.000981 AC XY: 73 AN XY: 74384

African (AFR) AF: 0.00378 AC: 157 AN: 41524

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.0000283 Hom.: 1865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10792821; hg19: chr11-85718641;