Variant chr11-121590137-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003105.6(SORL1):c.4176C>T(p.Asn1392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,614,016 control chromosomes in the GnomAD database, including 1,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 767 hom., cov: 33)

Exomes 𝑓: 0.023 ( 1034 hom. )

Consequence

SORL1
NM_003105.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.37

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-121590137-C-T is Benign according to our data. Variant chr11-121590137-C-T is described in ClinVar as [Benign]. Clinvar id is 1600983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121590137-C-T is described in Lovd as [Likely_benign]. Variant chr11-121590137-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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.4176C>T	p.Asn1392=	synonymous_variant	30/48	ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SORL1	ENST00000260197.12 linkuse as main transcript	c.4176C>T	p.Asn1392=	synonymous_variant	30/48	1	NM_003105.6	P1
SORL1	ENST00000525532.5 linkuse as main transcript	c.1008C>T	p.Asn336=	synonymous_variant	10/28	2
SORL1	ENST00000534286.5 linkuse as main transcript	c.906C>T	p.Asn302=	synonymous_variant	7/25	2
SORL1	ENST00000532694.5 linkuse as main transcript	c.714C>T	p.Asn238=	synonymous_variant	7/25	2

Frequencies

GnomAD3 genomes

AF:

0.0667

AC:

10146

AN:

152112

Hom.:

767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0645

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0317

AC:

7984

AN:

251474

Hom.:

395

AF XY:

0.0284

AC XY:

3854

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.0561

Gnomad SAS exome

AF:

0.0219

Gnomad FIN exome

AF:

0.00919

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0232

AC:

33874

AN:

1461786

Hom.:

1034

Cov.:

AF XY:

0.0225

AC XY:

16387

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0790

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.00867

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0279

GnomAD4 genome

AF:

0.0667

AC:

10157

AN:

152230

Hom.:

767

Cov.:

AF XY:

0.0646

AC XY:

4807

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.0349

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0304

Hom.:

256

Bravo

AF:

0.0738

Asia WGS

AF:

0.0470

AC:

162

AN:

3478

EpiCase

AF:

0.0188

EpiControl

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SORL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 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). -

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

-0.45

CADD

Benign

6.1

DANN

Benign

0.85

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