2-86214180-A-C

Position:

• chr2-86214180-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001371279.1(REEP1):​c.*2859T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 153,594 control chromosomes in the GnomAD database, including 9,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9441 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.861

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-86214180-A-C is Benign according to our data. Variant chr2-86214180-A-C is described in ClinVar as [Benign]. Clinvar id is 337344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP1	NM_001371279.1	c.*2859T>G		3_prime_UTR_variant	9/9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7	c.*2859T>G		3_prime_UTR_variant	9/9	5	NM_001371279.1	ENSP00000438346
REEP1	ENST00000165698.9	c.*2920T>G		3_prime_UTR_variant	7/7	1		ENSP00000165698	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48734 AN: 152006 Hom.: 9429 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.431 AC: 634 AN: 1470 Hom.: 136 Cov.: 0 AF XY: 0.432 AC XY: 374 AN XY: 866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.320 AC: 48749 AN: 152124 Hom.: 9441 Cov.: 32 AF XY: 0.327 AC XY: 24343 AN XY: 74372

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.361

Alfa AF: 0.283 Hom.: 1743

Bravo AF: 0.322

Asia WGS AF: 0.477 AC: 1655 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Hereditary spastic paraplegia 31 Benign:1

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.73

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: rs708600; hg19: chr2-86441303;