5-145866399-C-G

Position:

• chr5-145866399-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080516.2(GRXCR2):​c.564+102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 712,772 control chromosomes in the GnomAD database, including 1,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (227 hom., cov: 33)
  • Exomes 𝑓: 0.057 (1186 hom.)
• Consequence: GRXCR2 NM_001080516.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.405

Genes affected

GRXCR2 (HGNC:33862): (glutaredoxin and cysteine rich domain containing 2) This gene encodes a protein containing a glutaredoxin domain, which functions in protein S-glutathionylation. A mutation in this gene was found in a family with autoosomal recessive nonsyndromic sensorineural deafness-101. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-145866399-C-G is Benign according to our data. Variant chr5-145866399-C-G is described in ClinVar as [Benign]. Clinvar id is 1274873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRXCR2	NM_001080516.2	c.564+102G>C		intron_variant		ENST00000377976.3	NP_001073985.1
GRXCR2	XM_017009708.2	c.276+102G>C		intron_variant			XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3	c.564+102G>C		intron_variant		2	NM_001080516.2	ENSP00000367214	P1
GRXCR2	ENST00000639411.1	c.159+102G>C		intron_variant		5		ENSP00000491860

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7224 AN: 152130 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0573 AC: 32094 AN: 560524 Hom.: 1186 AF XY: 0.0563 AC XY: 16667 AN XY: 295820

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0407

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.000173

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.0879

Gnomad4 NFE exome AF: 0.0700

Gnomad4 OTH exome AF: 0.0559

GnomAD4 genome AF: 0.0474 AC: 7222 AN: 152248 Hom.: 227 Cov.: 33 AF XY: 0.0475 AC XY: 3533 AN XY: 74442

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0472

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0544 Hom.: 29

Bravo AF: 0.0440

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.68

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: rs17423559; hg19: chr5-145245962;