rs783777

Variant names:

• chr5-149351655-G-A
• rs783777
• NM_152407.4:c.*373G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152407.4. 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
	GRPEL2	NM_152407.4	MANE Select	c.*373G>A		3_prime_UTR	Exon 4 of 4	NP_689620.2
	GRPEL2-AS1	NR_132366.1		n.119-3257C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRPEL2	ENST00000329271.8	TSL:1 MANE Select	c.*373G>A		3_prime_UTR	Exon 4 of 4	ENSP00000329558.3	Q8TAA5-1
	GRPEL2	ENST00000913747.1		c.*373G>A		3_prime_UTR	Exon 4 of 4	ENSP00000583806.1
	GRPEL2	ENST00000507562.1	TSL:3	n.1181G>A		non_coding_transcript_exon	Exon 4 of 4

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

African (AFR) AF: 0.0126 AC: 3 AN: 238

American (AMR) AF: 0.0771 AC: 144 AN: 1868

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 20 AN: 202

East Asian (EAS) AF: 0.0745 AC: 38 AN: 510

South Asian (SAS) AF: 0.0478 AC: 45 AN: 942

European-Finnish (FIN) AF: 0.141 AC: 29 AN: 206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 20

European-Non Finnish (NFE) AF: 0.151 AC: 857 AN: 5678

Other (OTH) AF: 0.108 AC: 53 AN: 492

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

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: 39 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11259 AN: 68016

Other (OTH) AF: 0.132 AC: 280 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.76
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs783777; hg19: chr5-148731218;