Variant chr2-86216945-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_001371279.1(REEP1):c.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,019,268 control chromosomes in the GnomAD database, including 506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.022 ( 69 hom., cov: 32)

Exomes 𝑓: 0.028 ( 437 hom. )

Consequence

REEP1
NM_001371279.1 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-86216945-A-G is Benign according to our data. Variant chr2-86216945-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 337385.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}. Variant chr2-86216945-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3318/152272) while in subpopulation NFE AF= 0.0336 (2286/68022). AF 95% confidence interval is 0.0325. There are 69 homozygotes in gnomad4. There are 1577 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP1	NM_001371279.1 link	c.*94T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924 link	c.*94T>C		3_prime_UTR_variant	Exon 9 of 9	5	NM_001371279.1	ENSP00000438346.3		A0A1C7CYY3

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3318

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0336

Gnomad OTH

AF:

0.0206

GnomAD4 exome

AF:

0.0278

AC:

24094

AN:

866996

Hom.:

437

Cov.:

AF XY:

0.0270

AC XY:

12115

AN XY:

448970

show subpopulations

Gnomad4 AFR exome

AF:

0.00575

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0347

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0218

AC:

3318

AN:

152272

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1577

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00595

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0336

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0288

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 11, 2017

- -

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

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over