rs1620003

Variant names:

• chr11-121602284-G-A
• rs1620003
• NM_003105.6:c.4520-1909G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121602284-G-A
• chr11-121602284-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.4520-1909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,106 control chromosomes in the GnomAD database, including 17,476 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 0.43 (17476 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003105.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1	NM_003105.6	MANE Select	c.4520-1909G>A		intron	N/A	NP_003096.2	Q92673

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1	ENST00000260197.12	TSL:1 MANE Select	c.4520-1909G>A		intron	N/A	ENSP00000260197.6	Q92673
	SORL1	ENST00000905166.1		c.4520-1909G>A		intron	N/A	ENSP00000575225.1
	SORL1	ENST00000905167.1		c.4403-1909G>A		intron	N/A	ENSP00000575226.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65626 AN: 151988 Hom.: 17483 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.431 AC: 65616 AN: 152106 Hom.: 17476 Cov.: 32 AF XY: 0.426 AC XY: 31648 AN XY: 74348

African (AFR) AF: 0.147 AC: 6092 AN: 41498

American (AMR) AF: 0.383 AC: 5860 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3468

East Asian (EAS) AF: 0.136 AC: 706 AN: 5178

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4818

European-Finnish (FIN) AF: 0.557 AC: 5886 AN: 10562

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41352 AN: 67962

Other (OTH) AF: 0.459 AC: 971 AN: 2114

Alfa AF: 0.517 Hom.: 17846

Bravo AF: 0.406

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.13
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: rs1620003; hg19: chr11-121472993;