rs4936632

Variant names:

• chr11-121465019-A-G
• rs4936632
• NM_003105.6:c.286-4988A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-121465019-A-G
• chr11-121465019-A-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.286-4988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,012 control chromosomes in the GnomAD database, including 16,982 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 0.47 (16982 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.286-4988A>G		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.286-4988A>G		intron_variant	Intron 1 of 47	1	NM_003105.6	ENSP00000260197.6
SORL1	ENST00000532451.1	n.238-4988A>G		intron_variant	Intron 1 of 14	1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71254 AN: 151894 Hom.: 16989 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.469 AC: 71255 AN: 152012 Hom.: 16982 Cov.: 32 AF XY: 0.470 AC XY: 34882 AN XY: 74294

African (AFR) AF: 0.374 AC: 15503 AN: 41434

American (AMR) AF: 0.519 AC: 7934 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5160

South Asian (SAS) AF: 0.467 AC: 2250 AN: 4820

European-Finnish (FIN) AF: 0.500 AC: 5284 AN: 10562

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34210 AN: 67962

Other (OTH) AF: 0.476 AC: 1004 AN: 2110

Alfa AF: 0.493 Hom.: 9020

Bravo AF: 0.465

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		-0.18
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: rs4936632; hg19: chr11-121335728;