rs754515125
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000044.6(AR):c.2450-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )
Failed GnomAD Quality Control
Consequence
AR
NM_000044.6 splice_region, intron
NM_000044.6 splice_region, intron
Scores
2
Splicing: ADA: 0.001973
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.731
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.2450-6C>A | splice_region_variant, intron_variant | ENST00000374690.9 | NP_000035.2 | |||
AR | NM_001011645.3 | c.854-6C>A | splice_region_variant, intron_variant | NP_001011645.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AR | ENST00000374690.9 | c.2450-6C>A | splice_region_variant, intron_variant | 1 | NM_000044.6 | ENSP00000363822.3 | ||||
AR | ENST00000396044.8 | c.2174-865C>A | intron_variant | 1 | ENSP00000379359.3 | |||||
AR | ENST00000396043.4 | n.*798-6C>A | splice_region_variant, intron_variant | 1 | ENSP00000379358.4 | |||||
AR | ENST00000612452.5 | n.2450-6C>A | splice_region_variant, intron_variant | 5 | ENSP00000484033.2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD3 exomes AF: 0.00000552 AC: 1AN: 181306Hom.: 0 AF XY: 0.0000151 AC XY: 1AN XY: 66166
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2AN: 1097417Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2AN XY: 362877
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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1097417
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GnomAD4 genome Cov.: 22
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Cov.:
22
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at