dbSNP rs12806: ERLIN1:c.*746T>C (chr10-100151385-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006459.4(ERLIN1):c.*746T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 153,102 control chromosomes in the GnomAD database, including 8,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 8256 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3 hom. )

Consequence

ERLIN1
NM_006459.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 62
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
amyotrophic lateral sclerosis
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ERLIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN1	NM_006459.4 link	c.*746T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000421367.7	NP_006450.2	O75477

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7 link	c.*746T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_006459.4	ENSP00000410964.2		O75477

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37482

AN:

151990

Hom.:

8221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.0644

AC:

AN:

994

Hom.:

Cov.:

AF XY:

0.0679

AC XY:

AN XY:

560

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.0789

AC:

AN:

114

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0833

AC:

AN:

European-Finnish (FIN)

AF:

0.0822

AC:

AN:

146

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0562

AC:

AN:

658

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.247

AC:

37570

AN:

152108

Hom.:

8256

Cov.:

AF XY:

0.249

AC XY:

18494

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.584

AC:

24186

AN:

41426

American (AMR)

AF:

0.155

AC:

2378

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

421

AN:

3466

East Asian (EAS)

AF:

0.394

AC:

2038

AN:

5176

South Asian (SAS)

AF:

0.193

AC:

931

AN:

4826

European-Finnish (FIN)

AF:

0.139

AC:

1474

AN:

10600

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5413

AN:

68012

Other (OTH)

AF:

0.220

AC:

463

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1088

2176

3263

4351

5439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.169

Hom.:

7880

Bravo

AF:

0.264

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.3

(source)

DANN

Benign

0.79

PhyloP100

0.074

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over