Variant 11-121577381-T-G 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.3561T>G(p.Ser1187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,609,520 control chromosomes in the GnomAD database, including 59,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5264 hom., cov: 33)

Exomes 𝑓: 0.26 ( 54169 hom. )

Consequence

SORL1
NM_003105.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.19

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:

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=-0.59).

BP6

Variant 11-121577381-T-G is Benign according to our data. Variant chr11-121577381-T-G is described in ClinVar as [Benign]. Clinvar id is 1210021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121577381-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6 linkuse as main transcript	c.3561T>G	p.Ser1187=	synonymous_variant	25/48	ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SORL1	ENST00000260197.12 linkuse as main transcript	c.3561T>G	p.Ser1187=	synonymous_variant	25/48	1	NM_003105.6	P1
SORL1	ENST00000525532.5 linkuse as main transcript	c.393T>G	p.Ser131=	synonymous_variant	5/28	2
SORL1	ENST00000534286.5 linkuse as main transcript	c.291T>G	p.Ser97=	synonymous_variant	2/25	2
SORL1	ENST00000532694.5 linkuse as main transcript	c.99T>G	p.Ser33=	synonymous_variant	2/25	2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35590

AN:

152042

Hom.:

5241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.321

AC:

79110

AN:

246584

Hom.:

15666

AF XY:

0.321

AC XY:

42743

AN XY:

133336

show subpopulations

Gnomad AFR exome

AF:

0.0994

Gnomad AMR exome

AF:

0.529

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.257

AC:

373866

AN:

1457360

Hom.:

54169

Cov.:

AF XY:

0.262

AC XY:

190010

AN XY:

724922

show subpopulations

Gnomad4 AFR exome

AF:

0.0942

Gnomad4 AMR exome

AF:

0.505

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.234

AC:

35630

AN:

152160

Hom.:

5264

Cov.:

AF XY:

0.245

AC XY:

18191

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.564

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.236

Hom.:

7502

Bravo

AF:

0.236

Asia WGS

AF:

0.505

AC:

1755

AN:

3478

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

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

-0.59

CADD

Benign

4.0

DANN

Benign

0.72

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