rs17217069

Positions:

• chrX-67616907-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.1617-26349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 111,229 control chromosomes in the GnomAD database, including 42 homozygotes. There are 791 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 0.024 (42 hom., 791 hem., cov: 22)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0237 (2638/111229) while in subpopulation NFE AF= 0.0326 (1726/52892). AF 95% confidence interval is 0.0314. There are 42 homozygotes in gnomad4. There are 791 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1617-26349G>A		intron_variant		ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1617-26349G>A		intron_variant		1	NM_000044.6	P1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 2637 AN: 111173 Hom.: 42 Cov.: 22 AF XY: 0.0237 AC XY: 791 AN XY: 33437

Gnomad AFR AF: 0.00525

Gnomad AMI AF: 0.0323

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000286

Gnomad SAS AF: 0.0152

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0378

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0237 AC: 2638 AN: 111229 Hom.: 42 Cov.: 22 AF XY: 0.0236 AC XY: 791 AN XY: 33503

Gnomad4 AFR AF: 0.00524

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000287

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0348

Alfa AF: 0.0312 Hom.: 179

Bravo AF: 0.0217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.77

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: rs17217069; hg19: chrX-66836749;