Genetic Variant ERLIN1:c.826-237delT (chr10-100152588-TA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_006459.4(ERLIN1):c.826-237delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 152,316 control chromosomes in the GnomAD database, including 47 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 47 hom., cov: 32)

Consequence

ERLIN1
NM_006459.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00600

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 10-100152588-TA-T is Benign according to our data. Variant chr10-100152588-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1703399.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1773/152316) while in subpopulation AFR AF = 0.0402 (1672/41564). AF 95% confidence interval is 0.0386. There are 47 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN1	NM_006459.4 link	c.826-237delT		intron_variant	Intron 10 of 10	ENST00000421367.7	NP_006450.2	O75477

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7 link	c.826-237delT		intron_variant	Intron 10 of 10	1	NM_006459.4	ENSP00000410964.2		O75477
ERLIN1	ENST00000407654.7 link	c.826-237delT		intron_variant	Intron 11 of 11	1		ENSP00000384900.3		O75477

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1763

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0116

AC:

1773

AN:

152316

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0402

AC:

0.0402271

AN:

0.0402271

Gnomad4 AMR

AF:

0.00471

AC:

0.00470588

AN:

0.00470588

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000621

AC:

0.000620861

AN:

0.000620861

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000882

AC:

0.0000882042

AN:

0.0000882042

Gnomad4 OTH

AF:

0.00851

AC:

0.00851466

AN:

0.00851466

Heterozygous variant carriers

163

245

326

408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00925

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00346

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

May 12, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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