rs1629493

Variant names:

• chr11-121606387-G-A
• rs1629493
• NM_003105.6:c.4949-458G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121606387-G-A
• chr11-121606387-G-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.4949-458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,070 control chromosomes in the GnomAD database, including 20,068 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 0.49 (20068 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 6 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.4949-458G>A		intron_variant	Intron 35 of 47	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.4949-458G>A		intron_variant	Intron 35 of 47	1	NM_003105.6	ENSP00000260197.6

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74331 AN: 151952 Hom.: 20071 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.489 AC: 74338 AN: 152070 Hom.: 20068 Cov.: 33 AF XY: 0.481 AC XY: 35726 AN XY: 74340

African (AFR) AF: 0.303 AC: 12581 AN: 41506

American (AMR) AF: 0.416 AC: 6357 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3466

East Asian (EAS) AF: 0.194 AC: 1004 AN: 5174

South Asian (SAS) AF: 0.372 AC: 1791 AN: 4814

European-Finnish (FIN) AF: 0.556 AC: 5871 AN: 10554

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42568 AN: 67956

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.502 Hom.: 3984

Bravo AF: 0.471

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		-0.76
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: rs1629493; hg19: chr11-121477096;