rs11600875

chr11-121486259-C-T

Variant summary

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

The NM_003105.6(SORL1):c.529-1773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,138 control chromosomes in the GnomAD database, including 1,014 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 0.10 (1014 hom., cov: 31)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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 (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.529-1773C>T		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.529-1773C>T		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000532451.1	n.481-1773C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15761 AN: 152020 Hom.: 1012 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.104 AC: 15771 AN: 152138 Hom.: 1014 Cov.: 31 AF XY: 0.100 AC XY: 7473 AN XY: 74388

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0664

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0868

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0924 Hom.: 347

Bravo AF: 0.112

Asia WGS AF: 0.0400 AC: 138 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	0.27
Dann	Benign	0.73

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: rs11600875; hg19: chr11-121356968;