11-121610698-C-T

Position:

• chr11-121610698-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.5240-378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 166,250 control chromosomes in the GnomAD database, including 8,746 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 0.30 (7894 hom., cov: 32)
  • Exomes 𝑓: 0.33 (852 hom.)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.5240-378C>T		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.5240-378C>T		intron_variant		1	NM_003105.6	ENSP00000260197.6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45266 AN: 151862 Hom.: 7874 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.335 AC: 4777 AN: 14268 Hom.: 852 Cov.: 0 AF XY: 0.337 AC XY: 2507 AN XY: 7434

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.298 AC: 45330 AN: 151982 Hom.: 7894 Cov.: 32 AF XY: 0.310 AC XY: 23021 AN XY: 74284

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.309

Alfa AF: 0.311 Hom.: 7712

Bravo AF: 0.293

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.014
DANN	Benign	0.69

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: rs726601; hg19: chr11-121481407;