10-100177437-T-G

Variant names:

• chr10-100177437-T-G
• rs17112705
• NM_006459.4:c.304+696A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006459.4(ERLIN1):​c.304+696A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN1	NM_006459.4	c.304+696A>C		intron_variant	Intron 4 of 10	ENST00000421367.7	NP_006450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN1	ENST00000421367.7	c.304+696A>C		intron_variant	Intron 4 of 10	1	NM_006459.4	ENSP00000410964.2
ERLIN1	ENST00000407654.7	c.304+696A>C		intron_variant	Intron 5 of 11	1		ENSP00000384900.3
ERLIN1	ENST00000370408.2	c.304+696A>C		intron_variant	Intron 5 of 10	5		ENSP00000359436.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.52
PhyloP100		-0.19

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;