10-100154828-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006459.4(ERLIN1):c.825+31_825+32insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,573,978 control chromosomes in the GnomAD database, including 269 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (251 hom.)
• Consequence: ERLIN1 NM_006459.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.291

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 -10 ACMG points.

• BP6: Variant 10-100154828-A-AT is Benign according to our data. Variant chr10-100154828-A-AT is described in ClinVar as [Benign]. Clinvar id is 1183221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4	c.825+31_825+32insA		intron_variant		ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7	c.825+31_825+32insA		intron_variant		1	NM_006459.4	P1
ERLIN1	ENST00000407654.7	c.825+31_825+32insA		intron_variant		1		P1
ERLIN1	ENST00000370408.2			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 754 AN: 152196 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00781

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0118 AC: 2930 AN: 248974 Hom.: 82 AF XY: 0.0138 AC XY: 1854 AN XY: 134554

Gnomad AFR exome AF: 0.000435

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00551

Gnomad EAS exome AF: 0.0588

Gnomad SAS exome AF: 0.0515

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00756

GnomAD4 exome AF: 0.00580 AC: 8241 AN: 1421664 Hom.: 251 Cov.: 25 AF XY: 0.00713 AC XY: 5060 AN XY: 709456

Gnomad4 AFR exome AF: 0.000428

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00675

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.0498

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.000952

Gnomad4 OTH exome AF: 0.00894

GnomAD4 genome AF: 0.00494 AC: 752 AN: 152314 Hom.: 18 Cov.: 32 AF XY: 0.00604 AC XY: 450 AN XY: 74496

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00781

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.0538

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.00421

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs142968412; hg19: chr10-101914585;