rs1337080

Variant names:

• chrX-67659077-G-A
• rs1337080
• NM_000044.6:c.1768+15670G>A

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 17 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000044.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AR	NM_000044.6	MANE Select	c.1768+15670G>A		intron	N/A	NP_000035.2
	AR	NM_001348063.1		c.1768+15670G>A		intron	N/A	NP_001334992.1
	AR	NM_001348061.1		c.1768+15670G>A		intron	N/A	NP_001334990.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AR	ENST00000374690.9	TSL:1 MANE Select	c.1768+15670G>A		intron	N/A	ENSP00000363822.3
	AR	ENST00000396044.8	TSL:1	c.1768+15670G>A		intron	N/A	ENSP00000379359.3
	AR	ENST00000504326.5	TSL:1	c.1768+15670G>A		intron	N/A	ENSP00000421155.1

Frequencies

GnomAD3 genomes AF: 0.862 AC: 94078 AN: 109196 Hom.: 29176 Cov.: 21

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

African (AFR) AF: 0.678 AC: 20286 AN: 29925

American (AMR) AF: 0.945 AC: 9607 AN: 10170

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 2498 AN: 2628

East Asian (EAS) AF: 0.999 AC: 3429 AN: 3433

South Asian (SAS) AF: 0.938 AC: 2306 AN: 2458

European-Finnish (FIN) AF: 0.934 AC: 5298 AN: 5671

Middle Eastern (MID) AF: 0.919 AC: 192 AN: 209

European-Non Finnish (NFE) AF: 0.923 AC: 48544 AN: 52575

Other (OTH) AF: 0.901 AC: 1349 AN: 1497

Alfa AF: 0.903 Hom.: 152450

Bravo AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.19
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs1337080; hg19: chrX-66878919;