2-86214989-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001371279.1(REEP1):c.*2049_*2050insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (9335 hom., cov: 0)
  • Exomes 𝑓: 0.32 (1 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.227

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-86214989-C-CA is Benign according to our data. Variant chr2-86214989-C-CA is described in ClinVar as [Benign]. Clinvar id is 337360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP1	NM_001371279.1	c.*2049_*2050insT		3_prime_UTR_variant	9/9	ENST00000538924.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP1	ENST00000538924.7	c.*2049_*2050insT		3_prime_UTR_variant	9/9	5	NM_001371279.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 44029 AN: 92098 Hom.: 9330 Cov.: 0

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.550

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.320 AC: 73 AN: 228 Hom.: 1 Cov.: 0 AF XY: 0.321 AC XY: 43 AN XY: 134

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.478 AC: 44025 AN: 92112 Hom.: 9335 Cov.: 0 AF XY: 0.477 AC XY: 20554 AN XY: 43086

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.514

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs200132323; hg19: chr2-86442112;