Variant 2-86214554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001371279.1(REEP1):c.*2485G>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 0.0024 in 152,346 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)

Consequence

REEP1
NM_001371279.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-86214554-C-T is Benign according to our data. Variant chr2-86214554-C-T is described in ClinVar as [Benign]. Clinvar id is 337352.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0024 (366/152346) while in subpopulation AFR AF= 0.00839 (349/41588). AF 95% confidence interval is 0.00767. There are 3 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP1	NM_001371279.1 linkuse as main transcript	c.*2485G>A		3_prime_UTR_variant	9/9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7 linkuse as main transcript	c.*2485G>A	3_prime_UTR_variant	9/9	5	NM_001371279.1	ENSP00000438346
REEP1	ENST00000165698.9 linkuse as main transcript	c.*2546G>A	3_prime_UTR_variant	7/7	1		ENSP00000165698	P1	Q9H902-1
REEP1	ENST00000646181.1 linkuse as main transcript	n.3025G>A	non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

366

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00842

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00240

AC:

366

AN:

152346

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00839

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00324

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 31

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.75

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