rs138164407

Positions:

chr8-37751672-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_007175.8(ERLIN2):c.696G>A(p.Lys232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,613,940 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 23 hom. )

Consequence

ERLIN2
NM_007175.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.331

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 8-37751672-G-A is Benign according to our data. Variant chr8-37751672-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.331 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00308 (469/152374) while in subpopulation NFE AF= 0.00579 (394/68032). AF 95% confidence interval is 0.00532. There are 4 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ERLIN2	NM_007175.8 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	10/12	ENST00000519638.3	NP_009106.1
ERLIN2	NM_001362878.2 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	10/12		NP_001349807.1
ERLIN2	XM_047421307.1 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	11/13		XP_047277263.1
ERLIN2	XM_047421308.1 linkuse as main transcript	c.450G>A	p.Lys150=	synonymous_variant	7/9		XP_047277264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLIN2	ENST00000519638.3 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	10/12	2	NM_007175.8	ENSP00000428112	P1	O94905-1
ERLIN2	ENST00000521644.5 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	10/12	5		ENSP00000429621
ERLIN2	ENST00000518526.5 linkuse as main transcript	c.567G>A	p.Lys189=	synonymous_variant	8/8	3		ENSP00000429229

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

469

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00579

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00315

AC:

791

AN:

251072

Hom.:

AF XY:

0.00322

AC XY:

437

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00539

AC:

7876

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

3800

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00199

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.00648

Gnomad4 OTH exome

AF:

0.00469

GnomAD4 genome

AF:

0.00308

AC:

469

AN:

152374

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

200

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.00271

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00504

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ERLIN2: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2014

- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.7

DANN

Benign

0.79

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over