2-86337544-GCGGCT-GCGGCTCGGCT

Position:

• chr2-86337544-GCGGCT-GCGGCTCGGCT

Variant summary

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

The NM_001371279.1(REEP1):​c.-35_-34insAGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00874 in 1,236,372 control chromosomes in the GnomAD database, including 759 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (487 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (272 hom.)
• Consequence: REEP1 NM_001371279.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.468

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 2-86337544-G-GCGGCT is Benign according to our data. Variant chr2-86337544-G-GCGGCT is described in ClinVar as [Benign]. Clinvar id is 337388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP1	NM_001371279.1	c.-35_-34insAGCCG		5_prime_UTR_variant	1/9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7	c.-35_-34insAGCCG		5_prime_UTR_variant	1/9	5	NM_001371279.1	ENSP00000438346

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6557 AN: 150320 Hom.: 485 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000594

Gnomad OTH AF: 0.0266

GnomAD3 exomes AF: 0.00408 AC: 29 AN: 7110 Hom.: 1 AF XY: 0.00300 AC XY: 11 AN XY: 3670

Gnomad AFR exome AF: 0.0453

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00390 AC: 4239 AN: 1085946 Hom.: 272 Cov.: 30 AF XY: 0.00350 AC XY: 1829 AN XY: 522366

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.00834

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000457

Gnomad4 OTH exome AF: 0.00919

GnomAD4 genome AF: 0.0437 AC: 6573 AN: 150426 Hom.: 487 Cov.: 31 AF XY: 0.0418 AC XY: 3074 AN XY: 73498

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000594

Gnomad4 OTH AF: 0.0263

Alfa AF: 0.0385 Hom.: 14

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 19, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2014	The variant is found in MITONUC-MITOP panel(s). -

Spastic paraplegia, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs544099237; hg19: chr2-86564667;