NM_015701.5:c.952G>C

Variant names:

• chr2-53808371-G-C
• rs2287345
• NM_015701.5:c.952G>C
• ERLEC1 p.Val318Leu

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 28 publications found

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: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]

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015701.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERLEC1	NM_015701.5	MANE Select	c.952G>C	p.Val318Leu	missense	Exon 9 of 14	NP_056516.2
	ERLEC1	NM_001127397.3		c.952G>C	p.Val318Leu	missense	Exon 9 of 13	NP_001120869.1	Q96DZ1-3
	GPR75-ASB3	NM_001164165.2		c.102-42786C>G		intron	N/A	NP_001157637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERLEC1	ENST00000185150.9	TSL:1 MANE Select	c.952G>C	p.Val318Leu	missense	Exon 9 of 14	ENSP00000185150.4	Q96DZ1-1
	ERLEC1	ENST00000378239.5	TSL:1	c.880-843G>C		intron	N/A	ENSP00000367485.5	Q96DZ1-2
	ERLEC1	ENST00000952242.1		c.979G>C	p.Val327Leu	missense	Exon 9 of 14	ENSP00000622301.1

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

GnomAD2 exomes AF: 0.0965 AC: 24243 AN: 251176 AF XY: 0.0941

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

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

GnomAD4 genome AF: 0.0781 AC: 11901 AN: 152300 Hom.: 508 Cov.: 33 AF XY: 0.0788 AC XY: 5868 AN XY: 74482

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4724 AN: 68024

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0750 Hom.: 386

Bravo AF: 0.0834

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 v4.9

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
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.16
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.076
Sift	Benign	0.87	T
Sift4G	Benign	0.76	T
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)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2287345;

hg19: chr2-54035508;

COSMIC: COSV51751877;