2-86214211-C-CTGTT

Variant summary

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

The NM_001371279.1(REEP1):c.*2827_*2828insAACA 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 0.32 (9336 hom., cov: 0)
  • Exomes 𝑓: 0.35 (44 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71

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 2-86214211-C-CTGTT is Benign according to our data. Variant chr2-86214211-C-CTGTT is described in ClinVar as [Benign]. Clinvar id is 337345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP1	NM_001371279.1	c.*2827_*2828insAACA		3_prime_UTR_variant	9/9	ENST00000538924.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP1	ENST00000538924.7	c.*2827_*2828insAACA		3_prime_UTR_variant	9/9	5	NM_001371279.1
REEP1	ENST00000165698.9	c.*2888_*2889insAACA		3_prime_UTR_variant	7/7	1		P1
REEP1	ENST00000646181.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48539 AN: 151810 Hom.: 9324 Cov.: 0

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.349 AC: 257 AN: 736 Hom.: 44 Cov.: 0 AF XY: 0.345 AC XY: 151 AN XY: 438

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.320 AC: 48555 AN: 151930 Hom.: 9336 Cov.: 0 AF XY: 0.326 AC XY: 24217 AN XY: 74252

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.361

Alfa AF: 0.333 Hom.: 1002

Bravo AF: 0.321

Asia WGS AF: 0.475 AC: 1647 AN: 3476

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397794472; hg19: chr2-86441334;