chr4-42893123-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001080476.3(GRXCR1):c.-144G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 880,506 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0075 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00087 ( 11 hom. )
Consequence
GRXCR1
NM_001080476.3 5_prime_UTR
NM_001080476.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.14
Genes affected
GRXCR1 (HGNC:31673): (glutaredoxin and cysteine rich domain containing 1) This gene is one of 60 loci associated with autosomal-recessive nonsyndromic hearing impairment. This gene encodes a protein which contains GRX-like domains; these domains play a role in the S-glutathionylation of proteins and may be involved in actin organization in hair cells. [provided by RefSeq, Sep 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 4-42893123-G-A is Benign according to our data. Variant chr4-42893123-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196127.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00747 (1136/152130) while in subpopulation AFR AF= 0.0255 (1058/41530). AF 95% confidence interval is 0.0242. There are 12 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRXCR1 | NM_001080476.3 | c.-144G>A | 5_prime_UTR_variant | 1/4 | ENST00000399770.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRXCR1 | ENST00000399770.3 | c.-144G>A | 5_prime_UTR_variant | 1/4 | 1 | NM_001080476.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00748 AC: 1137AN: 152012Hom.: 12 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1137
AN:
152012
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000869 AC: 633AN: 728376Hom.: 11 AF XY: 0.000731 AC XY: 282AN XY: 385828
GnomAD4 exome
AF:
AC:
633
AN:
728376
Hom.:
AF XY:
AC XY:
282
AN XY:
385828
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00747 AC: 1136AN: 152130Hom.: 12 Cov.: 32 AF XY: 0.00729 AC XY: 542AN XY: 74380
GnomAD4 genome
?
AF:
AC:
1136
AN:
152130
Hom.:
Cov.:
32
AF XY:
AC XY:
542
AN XY:
74380
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
6
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at