NM_006459.4:c.304+696A>G

Variant names:

• chr10-100177437-T-C
• rs17112705
• NM_006459.4:c.304+696A>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.304+696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,106 control chromosomes in the GnomAD database, including 8,772 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 0.30 (8772 hom., cov: 32)
• Consequence: ERLIN1 NM_006459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 15 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 (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006459.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERLIN1	NM_006459.4	MANE Select	c.304+696A>G		intron	N/A	NP_006450.2
	ERLIN1	NM_001100626.2		c.304+696A>G		intron	N/A	NP_001094096.1
	ERLIN1	NM_001347857.2		c.304+696A>G		intron	N/A	NP_001334786.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERLIN1	ENST00000421367.7	TSL:1 MANE Select	c.304+696A>G		intron	N/A	ENSP00000410964.2
	ERLIN1	ENST00000407654.7	TSL:1	c.304+696A>G		intron	N/A	ENSP00000384900.3
	ERLIN1	ENST00000370408.2	TSL:5	c.304+696A>G		intron	N/A	ENSP00000359436.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46244 AN: 151988 Hom.: 8764 Cov.: 32

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.304 AC: 46268 AN: 152106 Hom.: 8772 Cov.: 32 AF XY: 0.309 AC XY: 22960 AN XY: 74330

African (AFR) AF: 0.0695 AC: 2890 AN: 41556

American (AMR) AF: 0.422 AC: 6442 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2259 AN: 5162

South Asian (SAS) AF: 0.360 AC: 1735 AN: 4820

European-Finnish (FIN) AF: 0.420 AC: 4435 AN: 10554

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26343 AN: 67952

Other (OTH) AF: 0.313 AC: 661 AN: 2112

Alfa AF: 0.366 Hom.: 18594

Bravo AF: 0.296

Asia WGS AF: 0.358 AC: 1246 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		-0.19
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: rs17112705; hg19: chr10-101937194;