chrX-67697425-C-T

Variant names:

• chrX-67697425-C-T
• rs1572501
• NM_000044.6:c.1885+11299C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000044.6(AR):​c.1885+11299C>T 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 0.98 (37438 hom., 31976 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 1 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=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6	c.1885+11299C>T		intron_variant	Intron 3 of 7	ENST00000374690.9	NP_000035.2
AR	NM_001011645.3	c.289+11299C>T		intron_variant	Intron 4 of 8		NP_001011645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.1885+11299C>T		intron_variant	Intron 3 of 7	1	NM_000044.6	ENSP00000363822.3
AR	ENST00000396044.8	c.1885+11299C>T		intron_variant	Intron 3 of 4	1		ENSP00000379359.3
AR	ENST00000396043.4	n.*233+11299C>T		intron_variant	Intron 4 of 8	1		ENSP00000379358.4
AR	ENST00000612452.5	n.1885+11299C>T		intron_variant	Intron 3 of 8	5		ENSP00000484033.2

Frequencies

GnomAD3 genomes AF: 0.981 AC: 108218 AN: 110260 Hom.: 37442 Cov.: 23

Gnomad AFR AF: 0.935

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.990

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: 0.981 AC: 108271 AN: 110316 Hom.: 37438 Cov.: 23 AF XY: 0.984 AC XY: 31976 AN XY: 32498

African (AFR) AF: 0.935 AC: 28368 AN: 30324

American (AMR) AF: 0.994 AC: 10216 AN: 10282

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2634 AN: 2634

East Asian (EAS) AF: 1.00 AC: 3482 AN: 3482

South Asian (SAS) AF: 1.00 AC: 2493 AN: 2494

European-Finnish (FIN) AF: 1.00 AC: 5823 AN: 5823

Middle Eastern (MID) AF: 1.00 AC: 215 AN: 215

European-Non Finnish (NFE) AF: 1.00 AC: 52871 AN: 52878

Other (OTH) AF: 0.990 AC: 1484 AN: 1499

Alfa AF: 0.992 Hom.: 12276

Bravo AF: 0.979

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.59
PhyloP100		-0.87
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: rs1572501; hg19: chrX-66917267;