X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGC
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000044.6(AR):c.1403_1420delGCGGCGGCGGCGGCGGCG(p.Gly468_Gly473del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 558,345 control chromosomes in the GnomAD database, including 1,198 homozygotes. There are 3,999 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 7 hom., 172 hem., cov: 0)
Exomes 𝑓: 0.028 ( 1191 hom. 3827 hem. )
Consequence
AR
NM_000044.6 disruptive_inframe_deletion
NM_000044.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.29
Genes affected
AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant X-67546514-TGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1168910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGC-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (912/83045) while in subpopulation NFE AF= 0.0142 (612/43129). AF 95% confidence interval is 0.0133. There are 7 homozygotes in gnomad4. There are 172 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.1403_1420delGCGGCGGCGGCGGCGGCG | p.Gly468_Gly473del | disruptive_inframe_deletion | Exon 1 of 8 | ENST00000374690.9 | NP_000035.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0110 AC: 912AN: 83041Hom.: 7 Cov.: 0 AF XY: 0.0104 AC XY: 172AN XY: 16605
GnomAD3 genomes
AF:
AC:
912
AN:
83041
Hom.:
Cov.:
0
AF XY:
AC XY:
172
AN XY:
16605
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:
GnomAD3 exomes AF: 0.0287 AC: 1079AN: 37570Hom.: 294 AF XY: 0.0225 AC XY: 292AN XY: 12980
GnomAD3 exomes
AF:
AC:
1079
AN:
37570
Hom.:
AF XY:
AC XY:
292
AN XY:
12980
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0276 AC: 13127AN: 475300Hom.: 1191 AF XY: 0.0325 AC XY: 3827AN XY: 117708
GnomAD4 exome
AF:
AC:
13127
AN:
475300
Hom.:
AF XY:
AC XY:
3827
AN XY:
117708
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: 0.0110 AC: 912AN: 83045Hom.: 7 Cov.: 0 AF XY: 0.0104 AC XY: 172AN XY: 16615
GnomAD4 genome
AF:
AC:
912
AN:
83045
Hom.:
Cov.:
0
AF XY:
AC XY:
172
AN XY:
16615
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
May 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
AR: BS1, BS2 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at