rs783777

Positions:

• chr5-149351655-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GRPEL2	NM_152407.4	c.*373G>A		3_prime_UTR_variant	4/4	ENST00000329271.8
GRPEL2-AS1	NR_132366.1	n.119-3257C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRPEL2	ENST00000329271.8	c.*373G>A		3_prime_UTR_variant	4/4	1	NM_152407.4	P1
GRPEL2-AS1	ENST00000521295.1	n.119-3257C>T		intron_variant, non_coding_transcript_variant		3
GRPEL2	ENST00000507562.1	n.1181G>A		non_coding_transcript_exon_variant	4/4	3
GRPEL2	ENST00000416916.2			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17084 AN: 152120 Hom.: 1312 Cov.: 33

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.: 0 AF XY: 0.115 AC XY: 598 AN XY: 5210

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0771

Gnomad4 ASJ exome AF: 0.0990

Gnomad4 EAS exome AF: 0.0745

Gnomad4 SAS exome AF: 0.0478

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.112 AC: 17084 AN: 152238 Hom.: 1312 Cov.: 33 AF XY: 0.109 AC XY: 8089 AN XY: 74430

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0961

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0781

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.132

Alfa AF: 0.152 Hom.: 2050

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
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs783777; hg19: chr5-148731218;