NM_001371279.1:c.*2049delT

Variant names:

• chr2-86214989-CA-C
• rs200132323
• NM_001371279.1:c.*2049delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001371279.1(REEP1):​c.*2049delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 0)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 2-86214989-CA-C is Benign according to our data. Variant chr2-86214989-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1190594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00484 (447/92282) while in subpopulation AFR AF = 0.0211 (375/17804). AF 95% confidence interval is 0.0193. There are 2 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.*2049delT		3_prime_UTR	Exon 9 of 9	NP_001358208.1	A0A1C7CYY3
	REEP1	NM_001410855.1		c.*2049delT		3_prime_UTR	Exon 8 of 8	NP_001397784.1	A0A2R8Y6K6
	REEP1	NM_001410856.1		c.*2110delT		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.*2049delT		3_prime_UTR	Exon 9 of 9	ENSP00000438346.3	A0A1C7CYY3
	REEP1	ENST00000165698.9	TSL:1	c.*2110delT		3_prime_UTR	Exon 7 of 7	ENSP00000165698.5	Q9H902-1
	REEP1	ENST00000908467.1		c.*2049delT		3_prime_UTR	Exon 9 of 9	ENSP00000578526.1

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 445 AN: 92268 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000373

Gnomad EAS AF: 0.000244

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00307

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000758

Gnomad OTH AF: 0.00233

GnomAD4 exome AF: 0.0391 AC: 9 AN: 230 Hom.: 0 Cov.: 0 AF XY: 0.0448 AC XY: 6 AN XY: 134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0354 AC: 8 AN: 226

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00484 AC: 447 AN: 92282 Hom.: 2 Cov.: 0 AF XY: 0.00524 AC XY: 226 AN XY: 43170

African (AFR) AF: 0.0211 AC: 375 AN: 17804

American (AMR) AF: 0.00216 AC: 20 AN: 9258

Ashkenazi Jewish (ASJ) AF: 0.000373 AC: 1 AN: 2678

East Asian (EAS) AF: 0.000245 AC: 1 AN: 4080

South Asian (SAS) AF: 0.00 AC: 0 AN: 3316

European-Finnish (FIN) AF: 0.00307 AC: 9 AN: 2932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.000758 AC: 38 AN: 50102

Other (OTH) AF: 0.00231 AC: 3 AN: 1300

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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: rs200132323; hg19: chr2-86442112;