rs5919411

chrX-67698871-A-GchrX-67698871-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000044.6(AR):c.1886-12531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.82 (27078 hom., 26780 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd at 27084 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1886-12531A>G		intron_variant		ENST00000374690.9
AR	NM_001011645.3	c.290-12531A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1886-12531A>G		intron_variant		1	NM_000044.6	P1
AR	ENST00000396044.8	c.1886-12531A>G		intron_variant		1
AR	ENST00000396043.4	c.*234-12531A>G		intron_variant, NMD_transcript_variant		1
AR	ENST00000612452.5	c.1886-12531A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.819 AC: 90122 AN: 110086 Hom.: 27084 Cov.: 22 AF XY: 0.827 AC XY: 26734 AN XY: 32340

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.819 AC: 90159 AN: 110145 Hom.: 27078 Cov.: 22 AF XY: 0.826 AC XY: 26780 AN XY: 32409

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.870

Alfa AF: 0.914 Hom.: 95958

Bravo AF: 0.810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs5919411; hg19: chrX-66918713;