X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGC
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000044.6(AR):c.1400_1420delGCGGCGGCGGCGGCGGCGGCG(p.Gly467_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 0.0128 in 558,215 control chromosomes in the GnomAD database, including 548 homozygotes. There are 2,000 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0062 ( 3 hom., 118 hem., cov: 0)
Exomes 𝑓: 0.014 ( 545 hom. 1882 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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1166508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGC-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00615 (511/83056) while in subpopulation AMR AF= 0.00832 (65/7816). AF 95% confidence interval is 0.00669. There are 3 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.1400_1420delGCGGCGGCGGCGGCGGCGGCG | p.Gly467_Gly473del | disruptive_inframe_deletion | Exon 1 of 8 | ENST00000374690.9 | NP_000035.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00609 AC: 506AN: 83052Hom.: 2 Cov.: 0 AF XY: 0.00704 AC XY: 117AN XY: 16616
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GnomAD3 exomes AF: 0.0121 AC: 455AN: 37570Hom.: 139 AF XY: 0.00840 AC XY: 109AN XY: 12980
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GnomAD4 exome AF: 0.0140 AC: 6641AN: 475159Hom.: 545 AF XY: 0.0160 AC XY: 1882AN XY: 117809
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GnomAD4 genome AF: 0.00615 AC: 511AN: 83056Hom.: 3 Cov.: 0 AF XY: 0.00710 AC XY: 118AN XY: 16626
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Apr 09, 2018
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Jan 15, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
Jan 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
AR: BS1, BS2 -
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at