dbSNP rs783777: GRPEL2:c.*373G>A (chr5-149351655-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152407.4(GRPEL2):c.*373G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 162,394 control chromosomes in the GnomAD database, including 1,416 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 0.11 ( 1312 hom., cov: 33)

Exomes 𝑓: 0.12 ( 104 hom. )

Consequence

GRPEL2
NM_152407.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

6 publications found

Variant links:

Genes affected

GRPEL2 (HGNC:21060): (GrpE like 2, mitochondrial) Predicted to enable adenyl-nucleotide exchange factor activity and unfolded protein binding activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GRPEL2 links:

GRPEL2-AS1 (HGNC:48999): (GRPEL2 antisense RNA 1)

GRPEL2-AS1 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPEL2	NM_152407.4 link	c.*373G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000329271.8	NP_689620.2	Q8TAA5-1
GRPEL2-AS1	NR_132366.1 link	n.119-3257C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRPEL2	ENST00000329271.8 link	c.*373G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_152407.4	ENSP00000329558.3		Q8TAA5-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17084

AN:

152120

Hom.:

1312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.0963

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0783

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.117

AC:

1189

AN:

10156

Hom.:

104

Cov.:

AF XY:

0.115

AC XY:

598

AN XY:

5210

show subpopulations

African (AFR)

AF:

0.0126

AC:

AN:

238

American (AMR)

AF:

0.0771

AC:

144

AN:

1868

Ashkenazi Jewish (ASJ)

AF:

0.0990

AC:

AN:

202

East Asian (EAS)

AF:

0.0745

AC:

AN:

510

South Asian (SAS)

AF:

0.0478

AC:

AN:

942

European-Finnish (FIN)

AF:

0.141

AC:

AN:

206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.151

AC:

857

AN:

5678

Other (OTH)

AF:

0.108

AC:

AN:

492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

157

210

262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.112

AC:

17084

AN:

152238

Hom.:

1312

Cov.:

AF XY:

0.109

AC XY:

8089

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0294

AC:

1223

AN:

41554

American (AMR)

AF:

0.0961

AC:

1469

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

494

AN:

3466

East Asian (EAS)

AF:

0.0781

AC:

405

AN:

5186

South Asian (SAS)

AF:

0.0471

AC:

227

AN:

4820

European-Finnish (FIN)

AF:

0.147

AC:

1553

AN:

10594

Middle Eastern (MID)

AF:

0.134

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.166

AC:

11259

AN:

68016

Other (OTH)

AF:

0.132

AC:

280

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

751

1502

2252

3003

3754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.146

Hom.:

2421

Bravo

AF:

0.106

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.32

(source)

DANN

Benign

0.76

PhyloP100

-0.17

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