chr11-121478402-A-G

Position:

• chr11-121478402-A-G

Variant summary

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

The ENST00000260197.12(SORL1):​c.528+159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,064 control chromosomes in the GnomAD database, including 8,045 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 (8045 hom., cov: 32)
• Consequence: SORL1 ENST00000260197.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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]

LOC105369535 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.528+159A>G		intron_variant		ENST00000260197.12	NP_003096.2
LOC105369535	NR_169501.2	n.471T>C		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.528+159A>G		intron_variant		1	NM_003105.6	ENSP00000260197	P1
SORL1	ENST00000532451.1	n.480+159A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46260 AN: 151946 Hom.: 8049 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.304 AC: 46239 AN: 152064 Hom.: 8045 Cov.: 32 AF XY: 0.302 AC XY: 22446 AN XY: 74316

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.305

Alfa AF: 0.346 Hom.: 1165

Bravo AF: 0.288

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.51

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: rs11218304; hg19: chr11-121349111;