rs12806

chr10-100151385-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006459.4(ERLIN1):c.*746T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 153,102 control chromosomes in the GnomAD database, including 8,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (8256 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3 hom.)
• Consequence: ERLIN1 NM_006459.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4	c.*746T>C		3_prime_UTR_variant	11/11	ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7	c.*746T>C		3_prime_UTR_variant	11/11	1	NM_006459.4	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37482 AN: 151990 Hom.: 8221 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.0644 AC: 64 AN: 994 Hom.: 3 Cov.: 0 AF XY: 0.0679 AC XY: 38 AN XY: 560

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.0789

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.0562

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.247 AC: 37570 AN: 152108 Hom.: 8256 Cov.: 32 AF XY: 0.249 AC XY: 18494 AN XY: 74372

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.220

Alfa AF: 0.119 Hom.: 1982

Bravo AF: 0.264

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.3
Dann	Benign	0.79

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: rs12806; hg19: chr10-101911142;