chrX-67546514-TGGCGGCGGCGGC-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000044.6(AR):​c.1409_1420delGCGGCGGCGGCG​(p.Gly470_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 0.074 in 555,074 control chromosomes in the GnomAD database, including 3,978 homozygotes. There are 10,692 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 80 hom., 688 hem., cov: 0)
Exomes 𝑓: 0.080 ( 3898 hom. 10004 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.29

Publications

6 publications found
Variant links:
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]
AR Gene-Disease associations (from GenCC):
  • androgen insensitivity syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
  • Kennedy disease
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • partial androgen insensitivity syndrome
    Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
  • complete androgen insensitivity syndrome
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6
Variant X-67546514-TGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.1409_1420delGCGGCGGCGGCG p.Gly470_Gly473del disruptive_inframe_deletion Exon 1 of 8 ENST00000374690.9 NP_000035.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARENST00000374690.9 linkc.1409_1420delGCGGCGGCGGCG p.Gly470_Gly473del disruptive_inframe_deletion Exon 1 of 8 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.0410
AC:
3405
AN:
83005
Hom.:
80
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0171
Gnomad AMI
AF:
0.0292
Gnomad AMR
AF:
0.0224
Gnomad ASJ
AF:
0.0284
Gnomad EAS
AF:
0.0405
Gnomad SAS
AF:
0.0242
Gnomad FIN
AF:
0.142
Gnomad MID
AF:
0.0359
Gnomad NFE
AF:
0.0523
Gnomad OTH
AF:
0.0406
GnomAD2 exomes
AF:
0.0598
AC:
2248
AN:
37570
AF XY:
0.0514
show subpopulations
Gnomad AFR exome
AF:
0.0617
Gnomad AMR exome
AF:
0.0482
Gnomad ASJ exome
AF:
0.0300
Gnomad EAS exome
AF:
0.240
Gnomad FIN exome
AF:
0.0994
Gnomad NFE exome
AF:
0.0534
Gnomad OTH exome
AF:
0.0588
GnomAD4 exome
AF:
0.0798
AC:
37682
AN:
472065
Hom.:
3898
AF XY:
0.0868
AC XY:
10004
AN XY:
115189
show subpopulations
African (AFR)
AF:
0.0258
AC:
336
AN:
13018
American (AMR)
AF:
0.0417
AC:
355
AN:
8509
Ashkenazi Jewish (ASJ)
AF:
0.0464
AC:
440
AN:
9478
East Asian (EAS)
AF:
0.0660
AC:
910
AN:
13788
South Asian (SAS)
AF:
0.0651
AC:
928
AN:
14264
European-Finnish (FIN)
AF:
0.156
AC:
3355
AN:
21547
Middle Eastern (MID)
AF:
0.0594
AC:
77
AN:
1297
European-Non Finnish (NFE)
AF:
0.0805
AC:
29750
AN:
369781
Other (OTH)
AF:
0.0751
AC:
1531
AN:
20383
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.581
Heterozygous variant carriers
0
562
1124
1685
2247
2809
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1024
2048
3072
4096
5120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0410
AC:
3403
AN:
83009
Hom.:
80
Cov.:
0
AF XY:
0.0415
AC XY:
688
AN XY:
16583
show subpopulations
African (AFR)
AF:
0.0172
AC:
373
AN:
21651
American (AMR)
AF:
0.0223
AC:
174
AN:
7815
Ashkenazi Jewish (ASJ)
AF:
0.0284
AC:
63
AN:
2222
East Asian (EAS)
AF:
0.0403
AC:
103
AN:
2559
South Asian (SAS)
AF:
0.0243
AC:
37
AN:
1522
European-Finnish (FIN)
AF:
0.142
AC:
336
AN:
2368
Middle Eastern (MID)
AF:
0.0345
AC:
6
AN:
174
European-Non Finnish (NFE)
AF:
0.0523
AC:
2253
AN:
43110
Other (OTH)
AF:
0.0400
AC:
43
AN:
1075
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
0
118
236
353
471
589
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
42
84
126
168
210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0324
Hom.:
327

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
May 19, 2020
Genetic Services Laboratory, University of Chicago
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 16, 2025
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
Oct 03, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Nov 12, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Androgen resistance syndrome Benign:1
May 18, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.3
Mutation Taster
=199/1
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs746853821; hg19: chrX-66766356; COSMIC: COSV65964523; API