rs661057

chr11-121458245-T-C

Variant summary

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

The NM_003105.6(SORL1):c.285+5629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,094 control chromosomes in the GnomAD database, including 13,147 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 0.41 (13147 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.285+5629T>C		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.285+5629T>C		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000532451.1	n.237+5629T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61730 AN: 151976 Hom.: 13128 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.406 AC: 61785 AN: 152094 Hom.: 13147 Cov.: 33 AF XY: 0.406 AC XY: 30215 AN XY: 74342

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.402

Alfa AF: 0.426 Hom.: 19921

Bravo AF: 0.392

Asia WGS AF: 0.512 AC: 1778 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	9.1
Dann	Benign	0.48

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: rs661057; hg19: chr11-121328954;