Variant 1-109342153-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002959.7(SORT1):c.969A>C(p.Thr323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,608,056 control chromosomes in the GnomAD database, including 419,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 33748 hom., cov: 32)

Exomes 𝑓: 0.72 ( 385683 hom. )

Consequence

SORT1
NM_002959.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.126

Variant links:

Genes affected

SORT1 (HGNC:11186): (sortilin 1) This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

SORT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-109342153-T-G is Benign according to our data. Variant chr1-109342153-T-G is described in ClinVar as [Benign]. Clinvar id is 3059338.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.126 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SORT1	NM_002959.7 linkuse as main transcript	c.969A>C	p.Thr323=	synonymous_variant	9/20	ENST00000256637.8
SORT1	NM_001205228.2 linkuse as main transcript	c.558A>C	p.Thr186=	synonymous_variant	9/20
SORT1	XM_005271100.3 linkuse as main transcript	c.966A>C	p.Thr322=	synonymous_variant	9/20
SORT1	XM_005271101.4 linkuse as main transcript	c.561A>C	p.Thr187=	synonymous_variant	9/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORT1	ENST00000256637.8 linkuse as main transcript	c.969A>C	p.Thr323=	synonymous_variant	9/20	1	NM_002959.7	P1	Q99523-1
SORT1	ENST00000538502.5 linkuse as main transcript	c.558A>C	p.Thr186=	synonymous_variant	9/20	2			Q99523-2

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98462

AN:

151950

Hom.:

33729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.777

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.958

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.699

GnomAD3 exomes

AF:

0.742

AC:

185917

AN:

250690

Hom.:

70648

AF XY:

0.742

AC XY:

100483

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.868

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.956

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.711

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.756

GnomAD4 exome

AF:

0.724

AC:

1053619

AN:

1455988

Hom.:

385683

Cov.:

AF XY:

0.724

AC XY:

524900

AN XY:

724610

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.859

Gnomad4 ASJ exome

AF:

0.837

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.711

Gnomad4 NFE exome

AF:

0.716

Gnomad4 OTH exome

AF:

0.723

GnomAD4 genome

AF:

0.648

AC:

98509

AN:

152068

Hom.:

33748

Cov.:

AF XY:

0.652

AC XY:

48478

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.411

Gnomad4 AMR

AF:

0.778

Gnomad4 ASJ

AF:

0.825

Gnomad4 EAS

AF:

0.959

Gnomad4 SAS

AF:

0.733

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.703

Alfa

AF:

0.667

Hom.:

16260

Bravo

AF:

0.648

Asia WGS

AF:

0.798

AC:

2771

AN:

3478

EpiCase

AF:

0.734

EpiControl

AF:

0.735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SORT1-related disorder

Benign:1

Benign, criteria provided, single submitter

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

-0.65

CADD

Benign

8.9

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

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