Variant chr1-109345810-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000256637.8(SORT1):c.904A>G(p.Lys302Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00277 in 1,613,876 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 11 hom. )

Consequence

SORT1
ENST00000256637.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.33

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009036541).

BP6

Variant 1-109345810-T-C is Benign according to our data. Variant chr1-109345810-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638980.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORT1	NM_002959.7 linkuse as main transcript	c.904A>G	p.Lys302Glu	missense_variant	8/20	ENST00000256637.8	NP_002950.3	Q99523-1
SORT1	NM_001205228.2 linkuse as main transcript	c.493A>G	p.Lys165Glu	missense_variant	8/20		NP_001192157.1	Q99523-2
SORT1	XM_005271100.3 linkuse as main transcript	c.901A>G	p.Lys301Glu	missense_variant	8/20		XP_005271157.1
SORT1	XM_005271101.4 linkuse as main transcript	c.496A>G	p.Lys166Glu	missense_variant	8/20		XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORT1	ENST00000256637.8 linkuse as main transcript	c.904A>G	p.Lys302Glu	missense_variant	8/20	1	NM_002959.7	ENSP00000256637.6		Q99523-1
SORT1	ENST00000538502.5 linkuse as main transcript	c.493A>G	p.Lys165Glu	missense_variant	8/20	2		ENSP00000438597.1		Q99523-2

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

361

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00290

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00263

AC:

662

AN:

251436

Hom.:

AF XY:

0.00265

AC XY:

360

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.00278

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00281

AC:

4103

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

2017

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.00296

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152296

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00154

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00213

AC:

258

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SORT1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.060

.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.16

Sift

Benign

0.10

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.49

.;P

Vest4

0.65

MVP

0.74

MPC

0.34

ClinPred

0.0089

GERP RS

5.8

Varity_R

0.29

gMVP

0.78

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