chrX-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000044.6(AR):​c.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG​(p.Gly461_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 0.0117 in 559,165 control chromosomes in the GnomAD database, including 430 homozygotes. There are 1,904 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 Benign (★). Synonymous variant affecting the same amino acid position (i.e. G461G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., 94 hem., cov: 0)
Exomes 𝑓: 0.013 ( 429 hom. 1810 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -10 ACMG points.

BP6
Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1299195.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00454 (377/83056) while in subpopulation NFE AF = 0.00686 (296/43135). AF 95% confidence interval is 0.00622. There are 1 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High Hemizygotes in GnomAd4 at 94 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly461_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.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly461_Gly473del disruptive_inframe_deletion Exon 1 of 8 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.00454
AC:
377
AN:
83052
Hom.:
1
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00116
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00410
Gnomad ASJ
AF:
0.00180
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00131
Gnomad FIN
AF:
0.00546
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00686
Gnomad OTH
AF:
0.00472
GnomAD2 exomes
AF:
0.0113
AC:
426
AN:
37570
AF XY:
0.0112
show subpopulations
Gnomad AFR exome
AF:
0.00363
Gnomad AMR exome
AF:
0.0102
Gnomad ASJ exome
AF:
0.00574
Gnomad EAS exome
AF:
0.00122
Gnomad FIN exome
AF:
0.00581
Gnomad NFE exome
AF:
0.0197
Gnomad OTH exome
AF:
0.0101
GnomAD4 exome
AF:
0.0130
AC:
6173
AN:
476109
Hom.:
429
AF XY:
0.0153
AC XY:
1810
AN XY:
118153
show subpopulations
African (AFR)
AF:
0.00129
AC:
17
AN:
13217
American (AMR)
AF:
0.00804
AC:
69
AN:
8580
Ashkenazi Jewish (ASJ)
AF:
0.00576
AC:
55
AN:
9546
East Asian (EAS)
AF:
0.000213
AC:
3
AN:
14089
South Asian (SAS)
AF:
0.00340
AC:
50
AN:
14715
European-Finnish (FIN)
AF:
0.00631
AC:
138
AN:
21860
Middle Eastern (MID)
AF:
0.00153
AC:
2
AN:
1305
European-Non Finnish (NFE)
AF:
0.0151
AC:
5612
AN:
372205
Other (OTH)
AF:
0.0110
AC:
227
AN:
20592
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.697
Heterozygous variant carriers
0
131
262
393
524
655
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
208
416
624
832
1040
<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:
0.00454
AC:
377
AN:
83056
Hom.:
1
Cov.:
0
AF XY:
0.00565
AC XY:
94
AN XY:
16626
show subpopulations
African (AFR)
AF:
0.00115
AC:
25
AN:
21655
American (AMR)
AF:
0.00410
AC:
32
AN:
7814
Ashkenazi Jewish (ASJ)
AF:
0.00180
AC:
4
AN:
2222
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2564
South Asian (SAS)
AF:
0.00131
AC:
2
AN:
1522
European-Finnish (FIN)
AF:
0.00546
AC:
13
AN:
2381
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
174
European-Non Finnish (NFE)
AF:
0.00686
AC:
296
AN:
43135
Other (OTH)
AF:
0.00465
AC:
5
AN:
1076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.521
Heterozygous variant carriers
0
10
20
31
41
51
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.00243
Hom.:
327
Bravo
AF:
0.00411

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 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

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: COSV65953555; API