10-100151918-T-C

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.*213A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 604,882 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (78 hom., cov: 32)
  • Exomes 𝑓: 0.025 (216 hom.)
• Consequence: ERLIN1 NM_006459.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.396

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=-0.61).
• BP6: Variant 10-100151918-T-C is Benign according to our data. Variant chr10-100151918-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1239192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4	c.*213A>G		3_prime_UTR_variant	11/11	ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7	c.*213A>G		3_prime_UTR_variant	11/11	1	NM_006459.4	P1
ERLIN1	ENST00000407654.7	c.*213A>G		3_prime_UTR_variant	12/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152144 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0251 AC: 11357 AN: 452620 Hom.: 216 Cov.: 0 AF XY: 0.0245 AC XY: 5928 AN XY: 242434

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.0527

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.0421

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.0676

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0228

GnomAD4 genome AF: 0.0269 AC: 4098 AN: 152262 Hom.: 78 Cov.: 32 AF XY: 0.0311 AC XY: 2315 AN XY: 74456

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0217 Hom.: 21

Bravo AF: 0.0246

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 25, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.1
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3802528; hg19: chr10-101911675;