Variant 14-95535046-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The variant allele was found at a frequency of 0.419 in 1,281,590 control chromosomes in the GnomAD database, including 114,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12693 hom., cov: 33)

Exomes 𝑓: 0.42 ( 101773 hom. )

Consequence

intergenic_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0110

Variant links:

Genes affected

(HGNC:):

links:

GLRX5 (HGNC:20134): (glutaredoxin 5) This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]

GLRX5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-95535046-A-C is Benign according to our data. Variant chr14-95535046-A-C is described in ClinVar as [Benign]. Clinvar id is 379973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.95535046A>C		intergenic_region
GLRX5	NM_016417.3 linkuse as main transcript	c.-44A>C		upstream_gene_variant		ENST00000331334.5	NP_057501.2	Q86SX6A0A384MDT9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000553672.1 linkuse as main transcript	n.301+1243A>C		intron_variant		2
GLRX5	ENST00000331334.5 linkuse as main transcript	c.-44A>C		upstream_gene_variant		1	NM_016417.3	ENSP00000328570.4		Q86SX6

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61509

AN:

151798

Hom.:

12695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.389

AC:

17584

AN:

45236

Hom.:

3619

AF XY:

0.398

AC XY:

10752

AN XY:

27034

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.440

Gnomad SAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.421

AC:

475771

AN:

1129674

Hom.:

101773

Cov.:

AF XY:

0.423

AC XY:

234587

AN XY:

554856

show subpopulations

Gnomad4 AFR exome

AF:

0.316

Gnomad4 AMR exome

AF:

0.373

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.405

AC:

61537

AN:

151916

Hom.:

12693

Cov.:

AF XY:

0.404

AC XY:

30005

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.403

Hom.:

10259

Bravo

AF:

0.403

Asia WGS

AF:

0.519

AC:

1803

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over