rs1629493

Positions:

• chr11-121606387-G-A

Variant summary

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

The NM_003105.6(SORL1):​c.4949-458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,070 control chromosomes in the GnomAD database, including 20,068 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 0.49 (20068 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.4949-458G>A		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.4949-458G>A		intron_variant		1	NM_003105.6	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74331 AN: 151952 Hom.: 20071 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.489 AC: 74338 AN: 152070 Hom.: 20068 Cov.: 33 AF XY: 0.481 AC XY: 35726 AN XY: 74340

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.505

Alfa AF: 0.508 Hom.: 3948

Bravo AF: 0.471

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.2
DANN	Benign	0.84

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: rs1629493; hg19: chr11-121477096;