X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
Variant names:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000044.6(AR):c.1418_1420delGCG(p.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 0.0218 in 461,058 control chromosomes in the GnomAD database, including 353 homozygotes. There are 1,662 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.061 ( 382 hom., 692 hem., cov: 0)
Exomes 𝑓: 0.022 ( 353 hom. 1662 hem. )
Failed GnomAD Quality Control
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-TGGC-T is Benign according to our data. Variant chrX-67546514-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGC-T is described in Lovd as [Likely_benign]. Variant chrX-67546514-TGGC-T is described in Lovd as [Likely_benign]. Variant chrX-67546514-TGGC-T is described in Lovd as [Benign].
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.1418_1420delGCG | p.Gly473del | disruptive_inframe_deletion | Exon 1 of 8 | ENST00000374690.9 | NP_000035.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0612 AC: 5078AN: 83002Hom.: 381 Cov.: 0 AF XY: 0.0419 AC XY: 696AN XY: 16614
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GnomAD4 exome AF: 0.0218 AC: 10065AN: 461058Hom.: 353 AF XY: 0.0150 AC XY: 1662AN XY: 110626
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0612 AC: 5078AN: 83006Hom.: 382 Cov.: 0 AF XY: 0.0416 AC XY: 692AN XY: 16624
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ClinVar
Significance: Benign/Likely 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
Nov 12, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
Sep 16, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at