10-100164661-T-C

Variant names:

• chr10-100164661-T-C
• rs10883451
• NM_006459.4:c.564-566A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006459.4(ERLIN1):​c.564-566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,126 control chromosomes in the GnomAD database, including 10,195 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 0.33 (10195 hom., cov: 32)
• Consequence: ERLIN1 NM_006459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN1	NM_006459.4	c.564-566A>G		intron_variant	Intron 7 of 10	ENST00000421367.7	NP_006450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7	c.564-566A>G		intron_variant	Intron 7 of 10	1	NM_006459.4	ENSP00000410964.2
ERLIN1	ENST00000407654.7	c.564-566A>G		intron_variant	Intron 8 of 11	1		ENSP00000384900.3
ERLIN1	ENST00000370408.2	c.564-566A>G		intron_variant	Intron 8 of 10	5		ENSP00000359436.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50262 AN: 152008 Hom.: 10197 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50253 AN: 152126 Hom.: 10195 Cov.: 32 AF XY: 0.322 AC XY: 23924 AN XY: 74370

African (AFR) AF: 0.126 AC: 5234 AN: 41504

American (AMR) AF: 0.325 AC: 4976 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3470

East Asian (EAS) AF: 0.0651 AC: 338 AN: 5190

South Asian (SAS) AF: 0.166 AC: 801 AN: 4830

European-Finnish (FIN) AF: 0.369 AC: 3892 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32566 AN: 67968

Other (OTH) AF: 0.345 AC: 728 AN: 2108

Alfa AF: 0.368 Hom.: 1714

Bravo AF: 0.318

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.66
PhyloP100		-0.92
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: rs10883451; hg19: chr10-101924418;