rs1792124

Positions:

• chr11-121570811-A-G
• chr11-121570811-A-T

Variant summary

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

The NM_003105.6(SORL1):​c.3337+541A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,284 control chromosomes in the GnomAD database, including 68,994 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 0.95 (68994 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.3337+541A>G		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.3337+541A>G		intron_variant		1	NM_003105.6	ENSP00000260197.6
SORL1	ENST00000525532.5	c.169+541A>G		intron_variant		2		ENSP00000434634.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144642 AN: 152166 Hom.: 68955 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.950 AC: 144740 AN: 152284 Hom.: 68994 Cov.: 33 AF XY: 0.953 AC XY: 70932 AN XY: 74462

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.992

Gnomad4 NFE AF: 0.982

Gnomad4 OTH AF: 0.965

Alfa AF: 0.964 Hom.: 27000

Bravo AF: 0.945

Asia WGS AF: 0.951 AC: 3304 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.82

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: rs1792124; hg19: chr11-121441520;