rs11218350

Positions:

• chr11-121581942-T-A
• chr11-121581942-T-G

Variant summary

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

The NM_003105.6(SORL1):​c.3581-1516T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,226 control chromosomes in the GnomAD database, including 5,203 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 0.23 (5203 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.3581-1516T>A		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.3581-1516T>A		intron_variant		1	NM_003105.6	ENSP00000260197	P1
SORL1	ENST00000525532.5	c.413-1516T>A		intron_variant		2		ENSP00000434634
SORL1	ENST00000532694.5	c.119-1516T>A		intron_variant		2		ENSP00000432131
SORL1	ENST00000534286.5	c.311-1516T>A		intron_variant		2		ENSP00000436447

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35522 AN: 152108 Hom.: 5179 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.234 AC: 35563 AN: 152226 Hom.: 5203 Cov.: 33 AF XY: 0.244 AC XY: 18184 AN XY: 74430

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.257

Alfa AF: 0.243 Hom.: 2812

Bravo AF: 0.236

Asia WGS AF: 0.503 AC: 1749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.89

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: rs11218350; hg19: chr11-121452651;