rs17217069

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000044.6(AR):​c.1617-26349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 111,229 control chromosomes in the GnomAD database, including 42 homozygotes. There are 791 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 42 hom., 791 hem., cov: 22)

Consequence

AR
NM_000044.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

3 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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0237 (2638/111229) while in subpopulation NFE AF = 0.0326 (1726/52892). AF 95% confidence interval is 0.0314. There are 42 homozygotes in GnomAd4. There are 791 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 42 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.1617-26349G>A intron_variant Intron 1 of 7 ENST00000374690.9 NP_000035.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARENST00000374690.9 linkc.1617-26349G>A intron_variant Intron 1 of 7 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.0237
AC:
2637
AN:
111173
Hom.:
42
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.00525
Gnomad AMI
AF:
0.0323
Gnomad AMR
AF:
0.0234
Gnomad ASJ
AF:
0.0159
Gnomad EAS
AF:
0.000286
Gnomad SAS
AF:
0.0152
Gnomad FIN
AF:
0.0565
Gnomad MID
AF:
0.0378
Gnomad NFE
AF:
0.0326
Gnomad OTH
AF:
0.0353
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0237
AC:
2638
AN:
111229
Hom.:
42
Cov.:
22
AF XY:
0.0236
AC XY:
791
AN XY:
33503
show subpopulations
African (AFR)
AF:
0.00524
AC:
161
AN:
30721
American (AMR)
AF:
0.0234
AC:
245
AN:
10461
Ashkenazi Jewish (ASJ)
AF:
0.0159
AC:
42
AN:
2642
East Asian (EAS)
AF:
0.000287
AC:
1
AN:
3486
South Asian (SAS)
AF:
0.0156
AC:
41
AN:
2628
European-Finnish (FIN)
AF:
0.0565
AC:
338
AN:
5978
Middle Eastern (MID)
AF:
0.0415
AC:
9
AN:
217
European-Non Finnish (NFE)
AF:
0.0326
AC:
1726
AN:
52892
Other (OTH)
AF:
0.0348
AC:
53
AN:
1522
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
92
184
275
367
459
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
32
64
96
128
160
<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:
0.0289
Hom.:
528
Bravo
AF:
0.0217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
7.4
DANN
Benign
0.77
PhyloP100
1.1
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs17217069; hg19: chrX-66836749; API