11-121631046-G-A

Position:

• chr11-121631046-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.*1483G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 154,146 control chromosomes in the GnomAD database, including 24,625 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 0.55 (24397 hom., cov: 32)
  • Exomes 𝑓: 0.46 (228 hom.)
• Consequence: SORL1 NM_003105.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.*1483G>A		3_prime_UTR_variant	48/48	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.*1483G>A		3_prime_UTR_variant	48/48	1	NM_003105.6	ENSP00000260197	P1
SORL1	ENST00000530365.1	n.759-970G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83106 AN: 151942 Hom.: 24343 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.460 AC: 959 AN: 2086 Hom.: 228 Cov.: 0 AF XY: 0.438 AC XY: 498 AN XY: 1138

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.547 AC: 83225 AN: 152060 Hom.: 24397 Cov.: 32 AF XY: 0.549 AC XY: 40772 AN XY: 74330

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.506

Alfa AF: 0.453 Hom.: 21562

Bravo AF: 0.564

Asia WGS AF: 0.661 AC: 2302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.69

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: rs1133174; hg19: chr11-121501755;