Genetic Variant NM_006459.4:c.826-85G>A (chr10-100152437-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006459.4(ERLIN1):c.826-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 806,732 control chromosomes in the GnomAD database, including 63,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 10022 hom., cov: 32)

Exomes 𝑓: 0.38 ( 53117 hom. )

Consequence

ERLIN1
NM_006459.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.416

Publications

19 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: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ERLIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-100152437-C-T is Benign according to our data. Variant chr10-100152437-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293005.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006459.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERLIN1	NM_006459.4	MANE Select	c.826-85G>A	intron	N/A	NP_006450.2	O75477
ERLIN1	NM_001100626.2		c.826-85G>A	intron	N/A	NP_001094096.1	O75477
ERLIN1	NM_001347857.2		c.826-85G>A	intron	N/A	NP_001334786.1	O75477

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERLIN1	ENST00000421367.7	TSL:1 MANE Select	c.826-85G>A	intron	N/A	ENSP00000410964.2	O75477
ERLIN1	ENST00000407654.7	TSL:1	c.826-85G>A	intron	N/A	ENSP00000384900.3	O75477
ERLIN1	ENST00000971770.1		c.700-85G>A	intron	N/A	ENSP00000641829.1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48936

AN:

151948

Hom.:

10024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.376

AC:

245937

AN:

654666

Hom.:

53117

AF XY:

0.370

AC XY:

129876

AN XY:

351156

show subpopulations

African (AFR)

AF:

0.0881

AC:

1630

AN:

18492

American (AMR)

AF:

0.253

AC:

10387

AN:

41080

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

6734

AN:

19606

East Asian (EAS)

AF:

0.0497

AC:

1789

AN:

36012

South Asian (SAS)

AF:

0.163

AC:

10860

AN:

66750

European-Finnish (FIN)

AF:

0.378

AC:

18768

AN:

49716

Middle Eastern (MID)

AF:

0.269

AC:

878

AN:

3266

European-Non Finnish (NFE)

AF:

0.472

AC:

182216

AN:

385984

Other (OTH)

AF:

0.375

AC:

12675

AN:

33760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6865

13730

20595

27460

34325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1544

3088

4632

6176

7720

<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:

0.322

AC:

48924

AN:

152066

Hom.:

10022

Cov.:

AF XY:

0.313

AC XY:

23295

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0972

AC:

4035

AN:

41510

American (AMR)

AF:

0.321

AC:

4905

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1208

AN:

3460

East Asian (EAS)

AF:

0.0653

AC:

338

AN:

5174

South Asian (SAS)

AF:

0.165

AC:

795

AN:

4820

European-Finnish (FIN)

AF:

0.369

AC:

3901

AN:

10572

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32521

AN:

67938

Other (OTH)

AF:

0.341

AC:

719

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1467

2934

4400

5867

7334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.364

Hom.:

2653

Bravo

AF:

0.309

Asia WGS

AF:

0.117

AC:

411

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

(source)

DANN

Benign

0.28

PhyloP100

-0.42

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over