Variant 10-100152307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006459.4(ERLIN1):c.871A>G(p.Ile291Val) variant causes a missense change. The variant allele was found at a frequency of 0.422 in 1,611,308 control chromosomes in the GnomAD database, including 158,534 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 10029 hom., cov: 32)

Exomes 𝑓: 0.43 ( 148505 hom. )

Consequence

ERLIN1
NM_006459.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.93

Variant links:

Genes affected

ERLIN1 (HGNC:16947): (ER lipid raft associated 1) The protein encoded by this gene is part of a protein complex that mediates degradation of inositol 1,4,5-trisphosphate receptors in the endoplasmic reticulum. The encoded protein also binds cholesterol and regulates the SREBP signaling pathway, which promotes cellular cholesterol homeostasis. Defects in this gene have been associated with spastic paraplegia 62. [provided by RefSeq, Dec 2016]

ERLIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010764897).

BP6

Variant 10-100152307-T-C is Benign according to our data. Variant chr10-100152307-T-C is described in ClinVar as [Benign]. Clinvar id is 1167054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4 linkuse as main transcript	c.871A>G	p.Ile291Val	missense_variant	11/11	ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7 linkuse as main transcript	c.871A>G	p.Ile291Val	missense_variant	11/11	1	NM_006459.4	P1
ERLIN1	ENST00000407654.7 linkuse as main transcript	c.871A>G	p.Ile291Val	missense_variant	12/12	1		P1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48963

AN:

152068

Hom.:

10031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0973

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0656

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.335

AC:

84196

AN:

251116

Hom.:

17313

AF XY:

0.339

AC XY:

46043

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.0874

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.0609

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.433

AC:

631454

AN:

1459122

Hom.:

148505

Cov.:

AF XY:

0.427

AC XY:

309690

AN XY:

726030

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.0511

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.493

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.322

AC:

48951

AN:

152186

Hom.:

10029

Cov.:

AF XY:

0.313

AC XY:

23317

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0970

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.0652

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.479

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.436

Hom.:

40253

Bravo

AF:

0.309

TwinsUK

AF:

0.505

AC:

1872

ALSPAC

AF:

0.496

AC:

1913

ESP6500AA

AF:

0.104

AC:

460

ESP6500EA

AF:

0.470

AC:

4044

ExAC

AF:

0.332

AC:

40348

Asia WGS

AF:

0.117

AC:

411

AN:

3478

EpiCase

AF:

0.469

EpiControl

AF:

0.475

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2021	- -

Hereditary spastic paraplegia 62

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.68

.;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.0000040

P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.061

Sift

Benign

0.14

T;T

Sift4G

Benign

0.15

T;T

Vest4

0.21

MPC

0.019

ClinPred

0.017

GERP RS

4.4

gMVP

0.50

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