NM_007175.8:c.318C>T

Variant names:

• chr8-37744590-C-T
• rs16887018
• NM_007175.8:c.318C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_007175.8(ERLIN2):​c.318C>T​(p.Asn106Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,614,062 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (138 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (132 hom.)
• Consequence: ERLIN2 NM_007175.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.37
• Publications: 3 publications found

Genes affected

ERLIN2 (HGNC:1356): (ER lipid raft associated 2) This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ERLIN2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 18

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• juvenile primary lateral sclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000183154 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 8-37744590-C-T is Benign according to our data. Variant chr8-37744590-C-T is described in ClinVar as Benign. ClinVar VariationId is 129021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007175.8. 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
	ERLIN2	NM_007175.8	MANE Select	c.318C>T	p.Asn106Asn	synonymous	Exon 6 of 12	NP_009106.1
	ERLIN2	NM_001362878.2		c.318C>T	p.Asn106Asn	synonymous	Exon 6 of 12	NP_001349807.1
	ERLIN2	NM_001003790.4		c.318C>T	p.Asn106Asn	synonymous	Exon 6 of 7	NP_001003790.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERLIN2	ENST00000519638.3	TSL:2 MANE Select	c.318C>T	p.Asn106Asn	synonymous	Exon 6 of 12	ENSP00000428112.1
	ERLIN2	ENST00000335171.10	TSL:1	c.318C>T	p.Asn106Asn	synonymous	Exon 6 of 7	ENSP00000335220.6
	ERLIN2	ENST00000963384.1		c.408C>T	p.Asn136Asn	synonymous	Exon 5 of 11	ENSP00000633443.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3576 AN: 152116 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00630 AC: 1585 AN: 251446 AF XY: 0.00473

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00269 AC: 3933 AN: 1461828 Hom.: 132 Cov.: 31 AF XY: 0.00240 AC XY: 1742 AN XY: 727220

African (AFR) AF: 0.0838 AC: 2805 AN: 33472

American (AMR) AF: 0.00487 AC: 218 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5766

European-Non Finnish (NFE) AF: 0.000468 AC: 520 AN: 1111964

Other (OTH) AF: 0.00518 AC: 313 AN: 60392

GnomAD4 genome AF: 0.0235 AC: 3577 AN: 152234 Hom.: 138 Cov.: 32 AF XY: 0.0221 AC XY: 1646 AN XY: 74420

African (AFR) AF: 0.0811 AC: 3366 AN: 41506

American (AMR) AF: 0.00720 AC: 110 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68032

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0131 Hom.: 51

Bravo AF: 0.0264

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00124

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		3.4
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16887018; hg19: chr8-37602108;