rs1408579

Variant names:

• chr10-100152437-C-T
• rs1408579
• NM_006459.4:c.826-85G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.416
• Publications: 19 publications found

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN1	NM_006459.4	c.826-85G>A		intron_variant	Intron 10 of 10	ENST00000421367.7	NP_006450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7	c.826-85G>A		intron_variant	Intron 10 of 10	1	NM_006459.4	ENSP00000410964.2
ERLIN1	ENST00000407654.7	c.826-85G>A		intron_variant	Intron 11 of 11	1		ENSP00000384900.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48936 AN: 151948 Hom.: 10024 Cov.: 32

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

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

GnomAD4 genome AF: 0.322 AC: 48924 AN: 152066 Hom.: 10022 Cov.: 32 AF XY: 0.313 AC XY: 23295 AN XY: 74346

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: 97 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32521 AN: 67938

Other (OTH) AF: 0.341 AC: 719 AN: 2106

Alfa AF: 0.364 Hom.: 2653

Bravo AF: 0.309

Asia WGS AF: 0.117 AC: 411 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.28
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1408579; hg19: chr10-101912194; COSMIC: COSV64941110; COSMIC: COSV64941110;