rs1503415

chr11-121615843-C-A

Variant summary

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

The NM_003105.6(SORL1):c.5604+788C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,002 control chromosomes in the GnomAD database, including 35,190 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 0.67 (35190 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.5604+788C>A		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.5604+788C>A		intron_variant		1	NM_003105.6	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102242 AN: 151884 Hom.: 35182 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.673 AC: 102281 AN: 152002 Hom.: 35190 Cov.: 32 AF XY: 0.663 AC XY: 49250 AN XY: 74288

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.669

Alfa AF: 0.669 Hom.: 15691

Bravo AF: 0.675

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.022
Dann	Benign	0.37

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: rs1503415; hg19: chr11-121486552;