NM_001371279.1:c.106-7T>G

Variant names:

• chr2-86264048-A-C
• rs373564876
• NM_001371279.1:c.106-7T>G

Variant summary

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

The NM_001371279.1(REEP1):​c.106-7T>G variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: REEP1 NM_001371279.1 splice_region, intron
• Scores: Splicing: ADA: 0.07285
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

REEP1 (HGNC:25786): (receptor accessory protein 1) This gene encodes a mitochondrial protein that functions to enhance the cell surface expression of odorant receptors. Mutations in this gene cause spastic paraplegia autosomal dominant type 31, a neurodegenerative disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

REEP1 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 31

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• neuronopathy, distal hereditary motor, type 5B

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuronopathy, distal hereditary motor, type 5A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spinal muscular atrophy, distal, autosomal recessive, 6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371279.1. 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
	REEP1	NM_001371279.1	MANE Select	c.106-7T>G		splice_region intron	N/A	NP_001358208.1
	REEP1	NM_001410855.1		c.106-7T>G		splice_region intron	N/A	NP_001397784.1
	REEP1	NM_001410856.1		c.106-7T>G		splice_region intron	N/A	NP_001397785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP1	ENST00000538924.7	TSL:5 MANE Select	c.106-7T>G		splice_region intron	N/A	ENSP00000438346.3
	REEP1	ENST00000165698.9	TSL:1	c.106-7T>G		splice_region intron	N/A	ENSP00000165698.5
	REEP1	ENST00000642243.1		c.64-7T>G		splice_region intron	N/A	ENSP00000494960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.073
dbscSNV1_RF	Benign	0.21
SpliceAI score (max)		0.080		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: rs373564876; hg19: chr2-86491171;