2-53808371-G-C

Position:

• chr2-53808371-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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]

GPR75-ASB3 (HGNC:):

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]

ACMG classification

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	UniProt
ERLEC1	NM_015701.5	c.952G>C	p.Val318Leu	missense_variant	9/14	ENST00000185150.9
GPR75-ASB3	NM_001164165.2	c.102-42786C>G		intron_variant
ERLEC1	NM_001127397.3	c.952G>C	p.Val318Leu	missense_variant	9/13
ERLEC1	NM_001127398.3	c.880-843G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLEC1	ENST00000185150.9	c.952G>C	p.Val318Leu	missense_variant	9/14	1	NM_015701.5	P3

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11896 AN: 152182 Hom.: 506 Cov.: 33

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

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.: 33 AF XY: 0.0752 AC XY: 54708 AN XY: 727166

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.: 33 AF XY: 0.0788 AC XY: 5868 AN XY: 74482

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	T
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	N
LIST_S2	Benign	0.58	T;T
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs2287345; hg19: chr2-54035508; COSMIC: COSV51751877;