rs17112705

Positions:

• chr10-100177437-T-C
• chr10-100177437-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4	c.304+696A>G		intron_variant		ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7	c.304+696A>G		intron_variant		1	NM_006459.4	P1
ERLIN1	ENST00000407654.7	c.304+696A>G		intron_variant		1		P1
ERLIN1	ENST00000370408.2	c.304+696A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.313

Alfa AF: 0.372 Hom.: 15136

Bravo AF: 0.296

Asia WGS AF: 0.358 AC: 1246 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45

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: rs17112705; hg19: chr10-101937194;