chrX-67546514-TGGCGGCGGCGGCGGC-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000044.6(AR):c.1406_1420delGCGGCGGCGGCGGCG(p.Gly469_Gly473del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 552,271 control chromosomes in the GnomAD database, including 427 homozygotes. There are 995 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G469G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0090 ( 7 hom., 156 hem., cov: 0)

Exomes 𝑓: 0.0078 ( 420 hom. 839 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.29

Publications

6 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

androgen insensitivity syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
Kennedy disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
partial androgen insensitivity syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
complete androgen insensitivity syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

AR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-67546514-TGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 434259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1406_1420delGCGGCGGCGGCGGCG	p.Gly469_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9 link	c.1406_1420delGCGGCGGCGGCGGCG	p.Gly469_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00903

AC:

750

AN:

83037

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00270

Gnomad EAS

AF:

0.00971

Gnomad SAS

AF:

0.00328

Gnomad FIN

AF:

0.00168

Gnomad MID

AF:

0.0205

Gnomad NFE

AF:

0.00267

Gnomad OTH

AF:

0.0189

GnomAD2 exomes

AF:

0.0106

AC:

397

AN:

37570

AF XY:

0.00539

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.00128

Gnomad EAS exome

AF:

0.0451

Gnomad FIN exome

AF:

0.00224

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.00784

AC:

3678

AN:

469230

Hom.:

420

AF XY:

0.00725

AC XY:

839

AN XY:

115712

show subpopulations

African (AFR)

AF:

0.0422

AC:

554

AN:

13140

American (AMR)

AF:

0.0148

AC:

125

AN:

8439

Ashkenazi Jewish (ASJ)

AF:

0.00276

AC:

AN:

9430

East Asian (EAS)

AF:

0.0544

AC:

741

AN:

13630

South Asian (SAS)

AF:

0.00650

AC:

AN:

14314

European-Finnish (FIN)

AF:

0.00295

AC:

AN:

20997

Middle Eastern (MID)

AF:

0.0117

AC:

AN:

1284

European-Non Finnish (NFE)

AF:

0.00509

AC:

1872

AN:

367792

Other (OTH)

AF:

0.00940

AC:

190

AN:

20204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00904

AC:

751

AN:

83041

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

156

AN XY:

16615

show subpopulations

African (AFR)

AF:

0.0244

AC:

527

AN:

21640

American (AMR)

AF:

0.00576

AC:

AN:

7817

Ashkenazi Jewish (ASJ)

AF:

0.00270

AC:

AN:

2222

East Asian (EAS)

AF:

0.00975

AC:

AN:

2564

South Asian (SAS)

AF:

0.00329

AC:

AN:

1521

European-Finnish (FIN)

AF:

0.00168

AC:

AN:

2379

Middle Eastern (MID)

AF:

0.0230

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00267

AC:

115

AN:

43135

Other (OTH)

AF:

0.0186

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00600

Hom.:

327

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 29, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AR: BS1 -

not specified

Benign:1

Jan 11, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AR-related disorder

Benign:1

Dec 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=199/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over