rs1361039

Positions:

• chrX-67653556-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000044.6(AR):​c.1768+10149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 111,372 control chromosomes in the GnomAD database, including 13 homozygotes. There are 433 hemizygotes in GnomAD. 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 0.012 (13 hom., 433 hem., cov: 22)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1301/111372) while in subpopulation NFE AF= 0.0163 (865/53082). AF 95% confidence interval is 0.0154. There are 13 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6	c.1768+10149G>A		intron_variant		ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.1768+10149G>A		intron_variant		1	NM_000044.6	ENSP00000363822.3

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1302 AN: 111320 Hom.: 13 Cov.: 22 AF XY: 0.0130 AC XY: 434 AN XY: 33490

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00278

Gnomad ASJ AF: 0.0155

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00267

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0212

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0117 AC: 1301 AN: 111372 Hom.: 13 Cov.: 22 AF XY: 0.0129 AC XY: 433 AN XY: 33552

Gnomad4 AFR AF: 0.00195

Gnomad4 AMR AF: 0.00278

Gnomad4 ASJ AF: 0.0155

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00268

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.0142 Hom.: 67

Bravo AF: 0.00838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.54

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: rs1361039; hg19: chrX-66873398;