GeneBe

rs746853821

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_000044.6(AR):​c.1379_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG​(p.Gly460_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 0.0000769 in 559,316 control chromosomes in the GnomAD database, including 7 homozygotes. There are 14 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., 3 hem., cov: 0)
Exomes 𝑓: 0.000082 ( 7 hom. 11 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.29
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2
High Hemizygotes in GnomAd4 at 3 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.1379_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly460_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.1379_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly460_Gly473del disruptive_inframe_deletion Exon 1 of 8 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.0000482
AC:
4
AN:
83058
Hom.:
0
Cov.:
0
AF XY:
0.000180
AC XY:
3
AN XY:
16622
show subpopulations
Gnomad AFR
AF:
0.0000462
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000384
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000819
AC:
39
AN:
476258
Hom.:
7
AF XY:
0.0000930
AC XY:
11
AN XY:
118246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000756
Gnomad4 AMR exome
AF:
0.000582
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000709
Gnomad4 SAS exome
AF:
0.000815
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000510
Gnomad4 OTH exome
AF:
0.0000485
GnomAD4 genome
AF:
0.0000482
AC:
4
AN:
83058
Hom.:
0
Cov.:
0
AF XY:
0.000180
AC XY:
3
AN XY:
16622
show subpopulations
Gnomad4 AFR
AF:
0.0000462
Gnomad4 AMR
AF:
0.000384
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs746853821; hg19: chrX-66766356; API