10-100154787-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006459.4(ERLIN1):c.825+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,170,272 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (38 hom., cov: 32)
  • Exomes 𝑓: 0.022 (355 hom.)
• Consequence: ERLIN1 NM_006459.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-100154787-T-C is Benign according to our data. Variant chr10-100154787-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1344930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2394/152294) while in subpopulation NFE AF= 0.0273 (1854/67998). AF 95% confidence interval is 0.0262. There are 38 homozygotes in gnomad4. There are 1072 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERLIN1	NM_006459.4	c.825+73A>G		intron_variant		ENST00000421367.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERLIN1	ENST00000421367.7	c.825+73A>G		intron_variant		1	NM_006459.4	P1
ERLIN1	ENST00000407654.7	c.825+73A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2394 AN: 152176 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00509

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.0222 AC: 22634 AN: 1017978 Hom.: 355 AF XY: 0.0214 AC XY: 11164 AN XY: 521404

Gnomad4 AFR exome AF: 0.00382

Gnomad4 AMR exome AF: 0.00583

Gnomad4 ASJ exome AF: 0.00270

Gnomad4 EAS exome AF: 0.0000541

Gnomad4 SAS exome AF: 0.00302

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0157 AC: 2394 AN: 152294 Hom.: 38 Cov.: 32 AF XY: 0.0144 AC XY: 1072 AN XY: 74480

Gnomad4 AFR AF: 0.00507

Gnomad4 AMR AF: 0.00947

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0209 Hom.: 7

Bravo AF: 0.0152

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.6
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41290524; hg19: chr10-101914544;