Variant chr5-145859720-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001080516.2(GRXCR2):c.*13G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,613,454 control chromosomes in the GnomAD database, including 1,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 105 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1199 hom. )

Consequence

GRXCR2
NM_001080516.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.206

Variant links:

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]

GRXCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 5-145859720-C-G is Benign according to our data. Variant chr5-145859720-C-G is described in ClinVar as [Benign]. Clinvar id is 1261199.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0277 (4219/152210) while in subpopulation NFE AF= 0.0415 (2822/67990). AF 95% confidence interval is 0.0402. There are 105 homozygotes in gnomad4. There are 2091 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 105 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRXCR2	NM_001080516.2 linkuse as main transcript	c.*13G>C		3_prime_UTR_variant	3/3	ENST00000377976.3	NP_001073985.1
GRXCR2	XM_017009708.2 linkuse as main transcript	c.*13G>C		3_prime_UTR_variant	3/3		XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3 linkuse as main transcript	c.*13G>C		3_prime_UTR_variant	3/3	2	NM_001080516.2	ENSP00000367214	P1
GRXCR2	ENST00000639411.1 linkuse as main transcript	c.*13G>C		3_prime_UTR_variant	4/4	5		ENSP00000491860

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4219

AN:

152092

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00659

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0628

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0288

AC:

7238

AN:

250908

Hom.:

160

AF XY:

0.0292

AC XY:

3966

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00629

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00820

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0311

GnomAD4 exome

AF:

0.0369

AC:

53912

AN:

1461244

Hom.:

1199

Cov.:

AF XY:

0.0362

AC XY:

26312

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00618

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00913

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.0423

Gnomad4 OTH exome

AF:

0.0303

GnomAD4 genome

AF:

0.0277

AC:

4219

AN:

152210

Hom.:

105

Cov.:

AF XY:

0.0281

AC XY:

2091

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00872

Gnomad4 FIN

AF:

0.0628

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0302

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.8

DANN

Benign

0.48

Splicing

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