rs1337078

Positions:

• chrX-67655199-A-G

Variant summary

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

The NM_000044.6(AR):​c.1768+11792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 109,786 control chromosomes in the GnomAD database, including 666 homozygotes. There are 1,900 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 0.068 (666 hom., 1900 hem., cov: 21)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6	c.1768+11792A>G		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+11792A>G		intron_variant		1	NM_000044.6	ENSP00000363822	P1

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 7480 AN: 109734 Hom.: 665 Cov.: 21 AF XY: 0.0586 AC XY: 1878 AN XY: 32064

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.000381

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000799

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.000815

Gnomad OTH AF: 0.0542

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

GnomAD4 genome AF: 0.0684 AC: 7509 AN: 109786 Hom.: 666 Cov.: 21 AF XY: 0.0591 AC XY: 1900 AN XY: 32126

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.000381

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000401

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000796

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0523 Hom.: 195

Bravo AF: 0.0794

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1337078; hg19: chrX-66875041;