Variant 10-100151918-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.*213A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 604,882 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 78 hom., cov: 32)

Exomes 𝑓: 0.025 ( 216 hom. )

Consequence

ERLIN1
NM_006459.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.396

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 10-100151918-T-C is Benign according to our data. Variant chr10-100151918-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1239192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0503 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.*213A>G		3_prime_UTR_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.*213A>G		3_prime_UTR_variant	11/11	1	NM_006459.4	P1
ERLIN1	ENST00000407654.7 linkuse as main transcript	c.*213A>G		3_prime_UTR_variant	12/12	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4102

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0745

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0251

AC:

11357

AN:

452620

Hom.:

216

Cov.:

AF XY:

0.0245

AC XY:

5928

AN XY:

242434

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.0527

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0421

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0676

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0269

AC:

4098

AN:

152262

Hom.:

Cov.:

AF XY:

0.0311

AC XY:

2315

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.0424

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0745

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2021	- -

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.1

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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