NM_001371279.1:c.*2824_*2827dupAACA

Variant names:

• chr2-86214211-C-CTGTT
• rs397794472
• NM_001371279.1:c.*2824_*2827dupAACA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001371279.1(REEP1):​c.*2824_*2827dupAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9336 hom., cov: 0)
  • Exomes 𝑓: 0.35 (44 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• 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 -16 ACMG points.

• BP6: Variant 2-86214211-C-CTGTT is Benign according to our data. Variant chr2-86214211-C-CTGTT is described in ClinVar as Benign. ClinVar VariationId is 337345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 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.*2824_*2827dupAACA		3_prime_UTR	Exon 9 of 9	NP_001358208.1	A0A1C7CYY3
	REEP1	NM_001410855.1		c.*2824_*2827dupAACA		3_prime_UTR	Exon 8 of 8	NP_001397784.1	A0A2R8Y6K6
	REEP1	NM_001410856.1		c.*2885_*2888dupAACA		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.*2824_*2827dupAACA		3_prime_UTR	Exon 9 of 9	ENSP00000438346.3	A0A1C7CYY3
	REEP1	ENST00000165698.9	TSL:1	c.*2885_*2888dupAACA		3_prime_UTR	Exon 7 of 7	ENSP00000165698.5	Q9H902-1
	REEP1	ENST00000908467.1		c.*2824_*2827dupAACA		3_prime_UTR	Exon 9 of 9	ENSP00000578526.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48539 AN: 151810 Hom.: 9324 Cov.: 0

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.349 AC: 257 AN: 736 Hom.: 44 Cov.: 0 AF XY: 0.345 AC XY: 151 AN XY: 438

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.583 AC: 7 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AF: 0.394 AC: 170 AN: 432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.278 AC: 74 AN: 266

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.320 AC: 48555 AN: 151930 Hom.: 9336 Cov.: 0 AF XY: 0.326 AC XY: 24217 AN XY: 74252

African (AFR) AF: 0.0964 AC: 4001 AN: 41492

American (AMR) AF: 0.450 AC: 6854 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3468

East Asian (EAS) AF: 0.581 AC: 2976 AN: 5120

South Asian (SAS) AF: 0.462 AC: 2231 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4261 AN: 10530

Middle Eastern (MID) AF: 0.393 AC: 114 AN: 290

European-Non Finnish (NFE) AF: 0.378 AC: 25714 AN: 67938

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.333 Hom.: 1002

Bravo AF: 0.321

Asia WGS AF: 0.475 AC: 1647 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spastic paraplegia, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397794472; hg19: chr2-86441334; COSMIC: COSV51255695; COSMIC: COSV51255695;