rs1204038

Positions:

• chrX-67568383-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000044.6(AR):​c.1616+21621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 110,698 control chromosomes in the GnomAD database, including 8,949 homozygotes. There are 10,288 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (8949 hom., 10288 hem., cov: 22)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.533

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-67568383-G-A is Benign according to our data. Variant chrX-67568383-G-A is described in ClinVar as [Benign]. Clinvar id is 1645141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1616+21621G>A		intron_variant		ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1616+21621G>A		intron_variant		1	NM_000044.6	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 37770 AN: 110644 Hom.: 8940 Cov.: 22 AF XY: 0.311 AC XY: 10238 AN XY: 32934

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00171

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.342 AC: 37832 AN: 110698 Hom.: 8949 Cov.: 22 AF XY: 0.312 AC XY: 10288 AN XY: 32998

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00171

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.291

Alfa AF: 0.231 Hom.: 2743

Bravo AF: 0.366

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Androgen resistance syndrome;C1839259:Kennedy disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.40

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: rs1204038; hg19: chrX-66788225;