Genetic Variant REEP5:c.521-3297G>C (chr5-112882132-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005669.5(REEP5):c.521-3297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 153,610 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 394 hom., cov: 31)

Exomes 𝑓: 0.096 ( 8 hom. )

Consequence

REEP5
NM_005669.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.107

Publications

2 publications found

Variant links:

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

REEP5 links:

SRP19 (HGNC:11300): (signal recognition particle 19) Enables 7S RNA binding activity. Contributes to ribosome binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Located in nucleolus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

SRP19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP5	NM_005669.5 link	c.521-3297G>C		intron_variant	Intron 4 of 4	ENST00000379638.9	NP_005660.4	Q00765-1
SRP19	NM_001204199.2 link	c.302-9471C>G		intron_variant	Intron 4 of 4		NP_001191128.1	A0A2U3TZN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9 link	c.521-3297G>C		intron_variant	Intron 4 of 4	1	NM_005669.5	ENSP00000368959.4		Q00765-1

Frequencies

GnomAD3 genomes

AF:

0.0654

AC:

9944

AN:

151972

Hom.:

395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0513

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0698

GnomAD4 exome

AF:

0.0962

AC:

146

AN:

1518

Hom.:

AF XY:

0.0926

AC XY:

AN XY:

788

show subpopulations

African (AFR)

AF:

0.0667

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0556

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.106

AC:

120

AN:

1130

European-Non Finnish (NFE)

AF:

0.0746

AC:

AN:

134

Other (OTH)

AF:

0.0625

AC:

AN:

128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0654

AC:

9949

AN:

152092

Hom.:

394

Cov.:

AF XY:

0.0651

AC XY:

4839

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0286

AC:

1185

AN:

41478

American (AMR)

AF:

0.0514

AC:

785

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3470

East Asian (EAS)

AF:

0.00501

AC:

AN:

5186

South Asian (SAS)

AF:

0.138

AC:

661

AN:

4796

European-Finnish (FIN)

AF:

0.0609

AC:

645

AN:

10596

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0902

AC:

6131

AN:

67986

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

481

962

1443

1924

2405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0472

Hom.:

Bravo

AF:

0.0616

Asia WGS

AF:

0.0610

AC:

210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.8

(source)

DANN

Benign

0.71

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over