2-53808371-G-C

Position:

chr2-53808371-G-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ERLEC1	NM_015701.5 link	c.952G>C	p.Val318Leu	missense_variant	9/14	ENST00000185150.9	NP_056516.2	Q96DZ1-1V9HWD3
ERLEC1	NM_001127397.3 link	c.952G>C	p.Val318Leu	missense_variant	9/13		NP_001120869.1	Q96DZ1-3
GPR75-ASB3	NM_001164165.2 link	c.102-42786C>G		intron_variant			NP_001157637.1	Q9Y575-3
ERLEC1	NM_001127398.3 link	c.880-843G>C		intron_variant			NP_001120870.1	Q96DZ1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLEC1	ENST00000185150.9 link	c.952G>C	p.Val318Leu	missense_variant	9/14	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

GnomAD3 exomes

AF:

0.0965

AC:

24243

AN:

251176

Hom.:

1498

AF XY:

0.0941

AC XY:

12777

AN XY:

135754

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 SAS exome

AF:

0.0992

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

Gnomad4 AFR exome

AF:

0.0623

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.0856

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0561

Gnomad4 NFE exome

AF:

0.0660

Gnomad4 OTH exome

AF:

0.0804

GnomAD4 genome

AF:

0.0781

AC:

11901

AN:

152300

Hom.:

508

Cov.:

AF XY:

0.0788

AC XY:

5868

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0908

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0535

Gnomad4 NFE

AF:

0.0694

Gnomad4 OTH

AF:

0.0856

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over