rs536360

Variant names:

• chr11-121457328-C-A
• rs536360
• NM_003105.6:c.285+4712C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121457328-C-A
• chr11-121457328-C-T

Variant summary

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

The NM_003105.6(SORL1):​c.285+4712C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,954 control chromosomes in the GnomAD database, including 21,740 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 0.52 (21740 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 3 publications found

Genes affected

SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

SORL1 Gene-Disease associations (from GenCC):

• early-onset autosomal dominant Alzheimer disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.285+4712C>A		intron_variant	Intron 1 of 47	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.285+4712C>A		intron_variant	Intron 1 of 47	1	NM_003105.6	ENSP00000260197.6
SORL1	ENST00000532451.1	n.237+4712C>A		intron_variant	Intron 1 of 14	1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79661 AN: 151838 Hom.: 21717 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.525 AC: 79726 AN: 151954 Hom.: 21740 Cov.: 32 AF XY: 0.527 AC XY: 39148 AN XY: 74248

African (AFR) AF: 0.383 AC: 15864 AN: 41414

American (AMR) AF: 0.638 AC: 9758 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3468

East Asian (EAS) AF: 0.702 AC: 3638 AN: 5182

South Asian (SAS) AF: 0.512 AC: 2460 AN: 4806

European-Finnish (FIN) AF: 0.600 AC: 6314 AN: 10532

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38062 AN: 67948

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.493 Hom.: 9400

Bravo AF: 0.523

Asia WGS AF: 0.619 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		0.060
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: rs536360; hg19: chr11-121328037;