rs617847

Variant names:

• chr11-121531934-G-A
• rs617847
• NM_003105.6:c.1597-530G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121531934-G-A
• chr11-121531934-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.1597-530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,982 control chromosomes in the GnomAD database, including 12,081 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 0.39 (12081 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.1597-530G>A		intron_variant	Intron 11 of 47	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.1597-530G>A		intron_variant	Intron 11 of 47	1	NM_003105.6	ENSP00000260197.6
SORL1	ENST00000532451.1	n.1549-530G>A		intron_variant	Intron 11 of 14	1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58778 AN: 151864 Hom.: 12052 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.387 AC: 58840 AN: 151982 Hom.: 12081 Cov.: 32 AF XY: 0.386 AC XY: 28671 AN XY: 74274

African (AFR) AF: 0.256 AC: 10598 AN: 41434

American (AMR) AF: 0.424 AC: 6472 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2909 AN: 5174

South Asian (SAS) AF: 0.441 AC: 2123 AN: 4818

European-Finnish (FIN) AF: 0.417 AC: 4398 AN: 10542

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29948 AN: 67960

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.396 Hom.: 2090

Bravo AF: 0.384

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.45
DANN	Benign	0.69
PhyloP100		-0.078
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: rs617847; hg19: chr11-121402643;