rs6589885

chr11-121555333-G-Achr11-121555333-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003105.6(SORL1):c.2571+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,612,496 control chromosomes in the GnomAD database, including 547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (103 hom., cov: 33)
  • Exomes 𝑓: 0.020 (444 hom.)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.46

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-121555333-G-A is Benign according to our data. Variant chr11-121555333-G-A is described in ClinVar as [Benign]. Clinvar id is 1548278.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-121555333-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.2571+15G>A		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.2571+15G>A		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000529445.1	n.277+15G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4627 AN: 152136 Hom.: 103 Cov.: 33

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0246 AC: 6153 AN: 250560 Hom.: 151 AF XY: 0.0236 AC XY: 3190 AN XY: 135454

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.00975

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0949

Gnomad SAS exome AF: 0.0223

Gnomad FIN exome AF: 0.00865

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.0196 AC: 28554 AN: 1460242 Hom.: 444 Cov.: 31 AF XY: 0.0195 AC XY: 14179 AN XY: 726438

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0120

Gnomad4 EAS exome AF: 0.0942

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.00816

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0205

GnomAD4 genome AF: 0.0304 AC: 4632 AN: 152254 Hom.: 103 Cov.: 33 AF XY: 0.0297 AC XY: 2209 AN XY: 74450

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.00792

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0262 Hom.: 19

Bravo AF: 0.0329

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0090
Dann	Benign	0.62

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: rs6589885; hg19: chr11-121426042; COSMIC: COSV52755363; COSMIC: COSV52755363;