chr8-37744590-C-T

Position:

• chr8-37744590-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERLIN2	NM_007175.8	c.318C>T	p.Asn106Asn	synonymous_variant	6/12	ENST00000519638.3	NP_009106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLIN2	ENST00000519638.3	c.318C>T	p.Asn106Asn	synonymous_variant	6/12	2	NM_007175.8	ENSP00000428112.1

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

GnomAD3 exomes AF: 0.00630 AC: 1585 AN: 251446 Hom.: 52 AF XY: 0.00473 AC XY: 643 AN XY: 135894

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 SAS exome AF: 0.000294

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

Gnomad4 AFR exome AF: 0.0838

Gnomad4 AMR exome AF: 0.00487

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000468

Gnomad4 OTH exome AF: 0.00518

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

Gnomad4 AFR AF: 0.0811

Gnomad4 AMR AF: 0.00720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0135 Hom.: 40

Bravo AF: 0.0264

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs16887018; hg19: chr8-37602108;