rs708600

Variant names:

• chr2-86214180-A-C
• rs708600
• NM_001371279.1:c.*2859T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-86214180-A-C
• chr2-86214180-A-G
• chr2-86214180-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 31

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• neuronopathy, distal hereditary motor, type 5B

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuronopathy, distal hereditary motor, type 5A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spinal muscular atrophy, distal, autosomal recessive, 6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371279.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP1	NM_001371279.1	MANE Select	c.*2859T>G		3_prime_UTR	Exon 9 of 9	NP_001358208.1	A0A1C7CYY3
	REEP1	NM_001410855.1		c.*2859T>G		3_prime_UTR	Exon 8 of 8	NP_001397784.1	A0A2R8Y6K6
	REEP1	NM_001410856.1		c.*2920T>G		3_prime_UTR	Exon 8 of 8	NP_001397785.1	A0A8I5QKJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP1	ENST00000538924.7	TSL:5 MANE Select	c.*2859T>G		3_prime_UTR	Exon 9 of 9	ENSP00000438346.3	A0A1C7CYY3
	REEP1	ENST00000165698.9	TSL:1	c.*2920T>G		3_prime_UTR	Exon 7 of 7	ENSP00000165698.5	Q9H902-1
	REEP1	ENST00000908467.1		c.*2859T>G		3_prime_UTR	Exon 9 of 9	ENSP00000578526.1

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.688 AC: 55 AN: 80

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.654 AC: 17 AN: 26

South Asian (SAS) AF: 0.438 AC: 28 AN: 64

European-Finnish (FIN) AF: 0.394 AC: 178 AN: 452

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.423 AC: 336 AN: 794

Other (OTH) AF: 0.425 AC: 17 AN: 40

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

African (AFR) AF: 0.0968 AC: 4019 AN: 41524

American (AMR) AF: 0.451 AC: 6894 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1366 AN: 3472

East Asian (EAS) AF: 0.587 AC: 3034 AN: 5168

South Asian (SAS) AF: 0.462 AC: 2230 AN: 4824

European-Finnish (FIN) AF: 0.407 AC: 4302 AN: 10582

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25748 AN: 67960

Other (OTH) AF: 0.361 AC: 764 AN: 2114

Alfa AF: 0.279 Hom.: 1745

Bravo AF: 0.322

Asia WGS AF: 0.477 AC: 1655 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary spastic paraplegia 31 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		-0.86
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs708600; hg19: chr2-86441303;