rs689021

chr11-121500411-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003105.6(SORL1):c.939+3362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,096 control chromosomes in the GnomAD database, including 12,689 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 0.40 (12689 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.939+3362G>A		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.939+3362G>A		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000532451.1	n.891+3362G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 61007 AN: 151978 Hom.: 12671 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.401 AC: 61054 AN: 152096 Hom.: 12689 Cov.: 33 AF XY: 0.401 AC XY: 29804 AN XY: 74364

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.409

Alfa AF: 0.429 Hom.: 6676

Bravo AF: 0.391

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs689021; hg19: chr11-121371120;