rs1010159

Positions:

• chr11-121612692-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.5323-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,396,550 control chromosomes in the GnomAD database, including 267,884 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 0.55 (24171 hom., cov: 32)
  • Exomes 𝑓: 0.62 (243713 hom.)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.5323-44C>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.5323-44C>T		intron_variant		1	NM_003105.6	ENSP00000260197.6

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84065 AN: 151874 Hom.: 24170 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.573

GnomAD3 exomes AF: 0.549 AC: 134707 AN: 245208 Hom.: 38651 AF XY: 0.550 AC XY: 72879 AN XY: 132436

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.652

Gnomad OTH exome AF: 0.591

GnomAD4 exome AF: 0.619 AC: 770072 AN: 1244560 Hom.: 243713 Cov.: 16 AF XY: 0.613 AC XY: 385998 AN XY: 629986

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.553 AC: 84074 AN: 151990 Hom.: 24171 Cov.: 32 AF XY: 0.545 AC XY: 40482 AN XY: 74286

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.567

Alfa AF: 0.595 Hom.: 7572

Bravo AF: 0.544

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.34
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1010159; hg19: chr11-121483401;