2-53808371-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015701.5(ERLEC1):c.952G>C(p.Val318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 1,614,000 control chromosomes in the GnomAD database, including 5,235 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V318A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.078 ( 508 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4727 hom. )

Consequence

ERLEC1
NM_015701.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.163

Publications

28 publications found

Variant links:

Genes affected

ERLEC1 (HGNC:25222): (endoplasmic reticulum lectin 1) This gene encodes a resident endoplasmic reticulum (ER) protein that functions in N-glycan recognition. This protein is thought to be involved in ER-associated degradation via its interaction with the membrane-associated ubiquitin ligase complex. It also functions as a regulator of multiple cellular stress-response pathways in a manner that promotes metastatic cell survival. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 21. [provided by RefSeq, Aug 2011]

ERLEC1 links:

GPR75-ASB3 (HGNC:40043): (GPR75-ASB3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring GPR75 (G protein-coupled receptor 75) and ASB3 (ankyrin repeat and SOCS box containing 3) on chromosome 2. The transcript includes exons from both GPR75 and ASB3 and translation initiates in the 5' non-coding exon of GPR75. The resulting protein has a novel N-terminus but is otherwise identical to that encoded by ASB3.[provided by RefSeq, Feb 2011]

GPR75-ASB3 links:

ASB3 (HGNC:16013): (ankyrin repeat and SOCS box containing 3) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2011]

ASB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012695193).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLEC1	NM_015701.5 link	c.952G>C	p.Val318Leu	missense_variant	Exon 9 of 14	ENST00000185150.9	NP_056516.2	Q96DZ1-1V9HWD3
ERLEC1	NM_001127397.3 link	c.952G>C	p.Val318Leu	missense_variant	Exon 9 of 13		NP_001120869.1	Q96DZ1-3
GPR75-ASB3	NM_001164165.2 link	c.102-42786C>G		intron_variant	Intron 1 of 9		NP_001157637.1	Q9Y575-3
ERLEC1	NM_001127398.3 link	c.880-843G>C		intron_variant	Intron 8 of 12		NP_001120870.1	Q96DZ1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLEC1	ENST00000185150.9 link	c.952G>C	p.Val318Leu	missense_variant	Exon 9 of 14	1	NM_015701.5	ENSP00000185150.4		Q96DZ1-1

Frequencies

GnomAD3 genomes

AF:

0.0782

AC:

11896

AN:

152182

Hom.:

506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0908

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0535

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0832

GnomAD2 exomes

AF:

0.0965

AC:

24243

AN:

251176

AF XY:

0.0941

show subpopulations

Gnomad AFR exome

AF:

0.0687

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.0545

Gnomad NFE exome

AF:

0.0711

Gnomad OTH exome

AF:

0.0937

GnomAD4 exome

AF:

0.0747

AC:

109167

AN:

1461700

Hom.:

4727

Cov.:

AF XY:

0.0752

AC XY:

54708

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0623

AC:

2087

AN:

33474

American (AMR)

AF:

0.166

AC:

7433

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0856

AC:

2238

AN:

26130

East Asian (EAS)

AF:

0.171

AC:

6767

AN:

39684

South Asian (SAS)

AF:

0.101

AC:

8752

AN:

86236

European-Finnish (FIN)

AF:

0.0561

AC:

2994

AN:

53402

Middle Eastern (MID)

AF:

0.113

AC:

649

AN:

5766

European-Non Finnish (NFE)

AF:

0.0660

AC:

73392

AN:

1111950

Other (OTH)

AF:

0.0804

AC:

4855

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5189

10378

15568

20757

25946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2864

5728

8592

11456

14320

<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:

0.0781

AC:

11901

AN:

152300

Hom.:

508

Cov.:

AF XY:

0.0788

AC XY:

5868

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0702

AC:

2919

AN:

41556

American (AMR)

AF:

0.113

AC:

1730

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0908

AC:

315

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

910

AN:

5186

South Asian (SAS)

AF:

0.103

AC:

497

AN:

4830

European-Finnish (FIN)

AF:

0.0535

AC:

568

AN:

10616

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0694

AC:

4724

AN:

68024

Other (OTH)

AF:

0.0856

AC:

181

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

571

1142

1712

2283

2854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0750

Hom.:

386

Bravo

AF:

0.0834

TwinsUK

AF:

0.0607

AC:

225

ALSPAC

AF:

0.0631

AC:

243

ESP6500AA

AF:

0.0667

AC:

294

ESP6500EA

AF:

0.0700

AC:

602

ExAC

AF:

0.0927

AC:

11255

Asia WGS

AF:

0.133

AC:

463

AN:

3478

EpiCase

AF:

0.0684

EpiControl

AF:

0.0746

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0070

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N

PhyloP100

-0.16

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.076

Sift

Benign

0.87

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0

.;B

Vest4

0.028

MutPred

0.12

Gain of catalytic residue at V318 (P = 0.068);Gain of catalytic residue at V318 (P = 0.068);

MPC

0.21

ClinPred

0.0028

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.14

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over