chr11-121615843-C-A

Variant names:

• chr11-121615843-C-A
• rs1503415
• NM_003105.6:c.5604+788C>A

Variant summary

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

The NM_003105.6(SORL1):​c.5604+788C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,002 control chromosomes in the GnomAD database, including 35,190 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 0.67 (35190 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.5604+788C>A		intron_variant	Intron 41 of 47	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.5604+788C>A		intron_variant	Intron 41 of 47	1	NM_003105.6	ENSP00000260197.6

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102242 AN: 151884 Hom.: 35182 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.673 AC: 102281 AN: 152002 Hom.: 35190 Cov.: 32 AF XY: 0.663 AC XY: 49250 AN XY: 74288

African (AFR) AF: 0.767 AC: 31814 AN: 41458

American (AMR) AF: 0.550 AC: 8403 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2640 AN: 3464

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5160

South Asian (SAS) AF: 0.440 AC: 2118 AN: 4810

European-Finnish (FIN) AF: 0.617 AC: 6505 AN: 10542

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46432 AN: 67978

Other (OTH) AF: 0.669 AC: 1408 AN: 2106

Alfa AF: 0.672 Hom.: 17744

Bravo AF: 0.675

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.022
DANN	Benign	0.37
PhyloP100		-0.82
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: rs1503415; hg19: chr11-121486552;