rs1620003

Positions:

• chr11-121602284-G-A
• chr11-121602284-G-T

Variant summary

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

The NM_003105.6(SORL1):​c.4520-1909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,106 control chromosomes in the GnomAD database, including 17,476 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 0.43 (17476 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.4520-1909G>A		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.4520-1909G>A		intron_variant		1	NM_003105.6	ENSP00000260197	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65626 AN: 151988 Hom.: 17483 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.431 AC: 65616 AN: 152106 Hom.: 17476 Cov.: 32 AF XY: 0.426 AC XY: 31648 AN XY: 74348

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.459

Alfa AF: 0.527 Hom.: 13244

Bravo AF: 0.406

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
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: rs1620003; hg19: chr11-121472993;