Genetic Variant NM_005669.5: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 Gene-Disease associations (from GenCC):

neutropenia
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005669.5. 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
	REEP5	NM_005669.5	MANE Select	c.521-3297G>C		intron	N/A	NP_005660.4
	SRP19	NM_001204199.2		c.302-9471C>G		intron	N/A	NP_001191128.1	A0A2U3TZN1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
REEP5	ENST00000379638.9	TSL:1 MANE Select	c.521-3297G>C	intron	N/A	ENSP00000368959.4	Q00765-1
REEP5	ENST00000497856.6	TSL:1	n.1029-3297G>C	intron	N/A
REEP5	ENST00000868806.1		c.548-3297G>C	intron	N/A	ENSP00000538865.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over