rs609903

Variant names:

• chr11-86029367-A-G
• rs609903
• NM_007166.4:c.273+2102T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-86029367-A-G
• chr11-86029367-A-T

Variant summary

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

The NM_007166.4(PICALM):​c.273+2102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,068 control chromosomes in the GnomAD database, including 37,135 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 0.70 (37135 hom., cov: 32)
• Consequence: PICALM NM_007166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4	c.273+2102T>C		intron_variant	Intron 2 of 19	ENST00000393346.8	NP_009097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8	c.273+2102T>C		intron_variant	Intron 2 of 19	1	NM_007166.4	ENSP00000377015.3

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105773 AN: 151950 Hom.: 37101 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.696 AC: 105859 AN: 152068 Hom.: 37135 Cov.: 32 AF XY: 0.689 AC XY: 51225 AN XY: 74328

African (AFR) AF: 0.793 AC: 32886 AN: 41494

American (AMR) AF: 0.631 AC: 9648 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2179 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3085 AN: 5170

South Asian (SAS) AF: 0.587 AC: 2828 AN: 4818

European-Finnish (FIN) AF: 0.647 AC: 6823 AN: 10550

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46234 AN: 67956

Other (OTH) AF: 0.688 AC: 1453 AN: 2112

Alfa AF: 0.682 Hom.: 140699

Bravo AF: 0.699

Asia WGS AF: 0.596 AC: 2074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.34
PhyloP100		0.46
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: rs609903; hg19: chr11-85740409;