chr4-7059492-T-C

Position:

• chr4-7059492-T-C

Variant summary

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

The NM_025196.4(GRPEL1):​c.*1370A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,248 control chromosomes in the GnomAD database, including 60,226 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 0.88 (60226 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GRPEL1 NM_025196.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

GRPEL1 (HGNC:19696): (GrpE like 1, mitochondrial) Enables identical protein binding activity and unfolded protein binding activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrial matrix and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRPEL1	NM_025196.4	c.*1370A>G		3_prime_UTR_variant	4/4	ENST00000264954.5	NP_079472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRPEL1	ENST00000264954.5	c.*1370A>G		3_prime_UTR_variant	4/4	1	NM_025196.4	ENSP00000264954	P1
GRPEL1	ENST00000706689.1	c.*1612A>G		3_prime_UTR_variant	3/3			ENSP00000516503
GRPEL1	ENST00000706688.1	c.*2017A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5			ENSP00000516502

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133877 AN: 152130 Hom.: 60213 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.892

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.880 AC: 133940 AN: 152248 Hom.: 60226 Cov.: 33 AF XY: 0.883 AC XY: 65760 AN XY: 74454

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.893

Alfa AF: 0.925 Hom.: 20876

Bravo AF: 0.868

Asia WGS AF: 0.965 AC: 3357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.46

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: rs4689584; hg19: chr4-7061219;