rs1337080

Positions:

• chrX-67659077-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000044.6(AR):​c.1768+15670G>A 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 0.86 (29173 hom., 27358 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1768+15670G>A		intron_variant		ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1768+15670G>A		intron_variant		1	NM_000044.6	P1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 94078 AN: 109196 Hom.: 29176 Cov.: 21 AF XY: 0.868 AC XY: 27311 AN XY: 31452

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.922

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.899

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: 0.862 AC: 94121 AN: 109245 Hom.: 29173 Cov.: 21 AF XY: 0.868 AC XY: 27358 AN XY: 31511

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.901

Alfa AF: 0.921 Hom.: 118037

Bravo AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.19

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: rs1337080; hg19: chrX-66878919;