rs1408579

Positions:

• chr10-100152437-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ERLIN1	NM_006459.4	c.826-85G>A		intron_variant		ENST00000421367.7	NP_006450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7	c.826-85G>A		intron_variant		1	NM_006459.4	ENSP00000410964	P1
ERLIN1	ENST00000407654.7	c.826-85G>A		intron_variant		1		ENSP00000384900	P1

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

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.0497

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.375

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

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.0653

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.341

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.28

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

Other links and lift over

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