2-86214526-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001371279.1(REEP1):c.*2513G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 152,788 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (68 hom., cov: 33)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.68

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 2-86214526-C-T is Benign according to our data. Variant chr2-86214526-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 337351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3318/152348) while in subpopulation NFE AF= 0.0336 (2283/68028). AF 95% confidence interval is 0.0324. There are 68 homozygotes in gnomad4. There are 1577 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 68 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP1	NM_001371279.1	c.*2513G>A		3_prime_UTR_variant	9/9	ENST00000538924.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP1	ENST00000538924.7	c.*2513G>A		3_prime_UTR_variant	9/9	5	NM_001371279.1
REEP1	ENST00000165698.9	c.*2574G>A		3_prime_UTR_variant	7/7	1		P1
REEP1	ENST00000646181.1	n.3053G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3318 AN: 152230 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0273 AC: 12 AN: 440 Hom.: 0 Cov.: 0 AF XY: 0.0187 AC XY: 5 AN XY: 268

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0218 AC: 3318 AN: 152348 Hom.: 68 Cov.: 33 AF XY: 0.0212 AC XY: 1577 AN XY: 74492

Gnomad4 AFR AF: 0.00591

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0299 Hom.: 21

Bravo AF: 0.0199

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 31 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	15
Dann	Benign	0.88

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: rs115098584; hg19: chr2-86441649;