1-109316863-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002959.7(SORT1):c.2237G>A(p.Ser746Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,606,016 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00047 ( 11 hom. )

Consequence

SORT1
NM_002959.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.554

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003215313).

BP6

Variant 1-109316863-C-T is Benign according to our data. Variant chr1-109316863-C-T is described in ClinVar as [Benign]. Clinvar id is 786468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00457 (696/152300) while in subpopulation AFR AF = 0.0162 (675/41560). AF 95% confidence interval is 0.0152. There are 5 homozygotes in GnomAd4. There are 313 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 696 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORT1	NM_002959.7 link	c.2237G>A	p.Ser746Asn	missense_variant	Exon 17 of 20	ENST00000256637.8	NP_002950.3	Q99523-1
SORT1	NM_001205228.2 link	c.1826G>A	p.Ser609Asn	missense_variant	Exon 17 of 20		NP_001192157.1	Q99523-2
SORT1	XM_005271100.3 link	c.2234G>A	p.Ser745Asn	missense_variant	Exon 17 of 20		XP_005271157.1
SORT1	XM_005271101.4 link	c.1829G>A	p.Ser610Asn	missense_variant	Exon 17 of 20		XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SORT1	ENST00000256637.8 link	c.2237G>A	p.Ser746Asn	missense_variant	Exon 17 of 20	1	NM_002959.7	ENSP00000256637.6	Q99523-1
SORT1	ENST00000538502.5 link	c.1826G>A	p.Ser609Asn	missense_variant	Exon 17 of 20	2		ENSP00000438597.1	Q99523-2
SORT1	ENST00000485149.1 link	n.65G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

694

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00128

AC:

315

AN:

246770

AF XY:

0.000923

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.000780

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000475

AC:

690

AN:

1453716

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

301

AN XY:

723262

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

AC:

597

AN:

33042

Gnomad4 AMR exome

AF:

0.000822

AC:

AN:

43800

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25990

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39432

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

84956

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53380

Gnomad4 NFE exome

AF:

0.00000993

AC:

AN:

1107242

Gnomad4 Remaining exome

AF:

0.000715

AC:

AN:

60138

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152300

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0162

AC:

0.0162416

AN:

0.0162416

Gnomad4 AMR

AF:

0.000981

AC:

0.000980777

AN:

0.000980777

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000588

AC:

0.0000588028

AN:

0.0000588028

Gnomad4 OTH

AF:

0.000946

AC:

0.000946074

AN:

0.000946074

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00512

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00165

AC:

200

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.092

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.14

Sift

Benign

0.68

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.0

.;B

Vest4

0.036

MVP

0.21

MPC

0.74

ClinPred

0.014

GERP RS

3.4

Varity_R

0.083

gMVP

0.72

Mutation Taster

=94/6

polymorphism

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