X-67557224-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000044.6(AR):​c.1616+10462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 110,501 control chromosomes in the GnomAD database, including 1,844 homozygotes. There are 5,603 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 0.19 ( 1844 hom., 5603 hem., cov: 22)

Consequence

AR
NM_000044.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Publications

10 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=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.1616+10462G>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.1616+10462G>A intron_variant Intron 1 of 7 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.190
AC:
20989
AN:
110447
Hom.:
1848
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.331
Gnomad AMI
AF:
0.119
Gnomad AMR
AF:
0.111
Gnomad ASJ
AF:
0.114
Gnomad EAS
AF:
0.00114
Gnomad SAS
AF:
0.0816
Gnomad FIN
AF:
0.111
Gnomad MID
AF:
0.169
Gnomad NFE
AF:
0.157
Gnomad OTH
AF:
0.175
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.190
AC:
20994
AN:
110501
Hom.:
1844
Cov.:
22
AF XY:
0.171
AC XY:
5603
AN XY:
32771
show subpopulations
African (AFR)
AF:
0.331
AC:
9988
AN:
30185
American (AMR)
AF:
0.111
AC:
1157
AN:
10444
Ashkenazi Jewish (ASJ)
AF:
0.114
AC:
301
AN:
2636
East Asian (EAS)
AF:
0.00114
AC:
4
AN:
3503
South Asian (SAS)
AF:
0.0811
AC:
210
AN:
2590
European-Finnish (FIN)
AF:
0.111
AC:
659
AN:
5927
Middle Eastern (MID)
AF:
0.172
AC:
37
AN:
215
European-Non Finnish (NFE)
AF:
0.157
AC:
8299
AN:
52824
Other (OTH)
AF:
0.172
AC:
258
AN:
1498
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
598
1196
1794
2392
2990
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
212
424
636
848
1060
<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:
0.155
Hom.:
5580
Bravo
AF:
0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.35
DANN
Benign
0.49
PhyloP100
0.065
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: rs12396249; hg19: chrX-66777066; API