rs1204040

Positions:

• chrX-67565906-C-A
• chrX-67565906-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000044.6(AR):​c.1616+19144C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 110,733 control chromosomes in the GnomAD database, including 4,493 homozygotes. There are 8,046 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 0.26 (4493 hom., 8046 hem., cov: 22)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1616+19144C>A		intron_variant		ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1616+19144C>A		intron_variant		1	NM_000044.6	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 29306 AN: 110683 Hom.: 4493 Cov.: 22 AF XY: 0.243 AC XY: 8018 AN XY: 32983

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00142

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.265 AC: 29339 AN: 110733 Hom.: 4493 Cov.: 22 AF XY: 0.244 AC XY: 8046 AN XY: 33043

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00143

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.227

Alfa AF: 0.0744 Hom.: 347

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.31

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: rs1204040; hg19: chrX-66785748;