Variant chr11-121496917-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003105.6(SORL1):c.807T>C(p.His269His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,612,730 control chromosomes in the GnomAD database, including 203,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19579 hom., cov: 29)

Exomes 𝑓: 0.50 ( 183699 hom. )

Consequence

SORL1
NM_003105.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.01

Variant links:

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]

SORL1 links:

SORL1 (HGNC:):

SORL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 11-121496917-T-C is Benign according to our data. Variant chr11-121496917-T-C is described in ClinVar as [Benign]. Clinvar id is 1209921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121496917-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6 linkuse as main transcript	c.807T>C	p.His269His	synonymous_variant	6/48	ENST00000260197.12	NP_003096.2	Q92673A0A024R3H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12 linkuse as main transcript	c.807T>C	p.His269His	synonymous_variant	6/48	1	NM_003105.6	ENSP00000260197.6		Q92673
SORL1	ENST00000532451.1 linkuse as main transcript	n.759T>C		non_coding_transcript_exon_variant	6/15	1

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76419

AN:

151450

Hom.:

19563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.489

AC:

122852

AN:

251272

Hom.:

30728

AF XY:

0.489

AC XY:

66385

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.532

GnomAD4 exome

AF:

0.500

AC:

730112

AN:

1461162

Hom.:

183699

Cov.:

AF XY:

0.499

AC XY:

362797

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.505

AC:

76471

AN:

151568

Hom.:

19579

Cov.:

AF XY:

0.505

AC XY:

37415

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.519

Hom.:

39354

Bravo

AF:

0.507

Asia WGS

AF:

0.372

AC:

1295

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.519

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

SORL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.74

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over