Variant 10-100154787-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006459.4(ERLIN1):c.825+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,170,272 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 38 hom., cov: 32)

Exomes 𝑓: 0.022 ( 355 hom. )

Consequence

ERLIN1
NM_006459.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.319

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-100154787-T-C is Benign according to our data. Variant chr10-100154787-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1344930.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2394/152294) while in subpopulation NFE AF= 0.0273 (1854/67998). AF 95% confidence interval is 0.0262. There are 38 homozygotes in gnomad4. There are 1072 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERLIN1	NM_006459.4 linkuse as main transcript	c.825+73A>G		intron_variant		ENST00000421367.7	NP_006450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7 linkuse as main transcript	c.825+73A>G		intron_variant		1	NM_006459.4	ENSP00000410964	P1
ERLIN1	ENST00000407654.7 linkuse as main transcript	c.825+73A>G		intron_variant		1		ENSP00000384900	P1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2394

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.0222

AC:

22634

AN:

1017978

Hom.:

355

AF XY:

0.0214

AC XY:

11164

AN XY:

521404

show subpopulations

Gnomad4 AFR exome

AF:

0.00382

Gnomad4 AMR exome

AF:

0.00583

Gnomad4 ASJ exome

AF:

0.00270

Gnomad4 EAS exome

AF:

0.0000541

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0286

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0157

AC:

2394

AN:

152294

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1072

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00507

Gnomad4 AMR

AF:

0.00947

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0273

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.6

DANN

Benign

0.42

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

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