X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000044.6(AR):c.231_239delGCAGCAGCA(p.Gln78_Gln80del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 982,901 control chromosomes in the GnomAD database, including 418 homozygotes. There are 3,243 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 308 hom., 647 hem., cov: 0)

Exomes 𝑓: 0.024 ( 110 hom. 2596 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.40

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000044.6

BP6

Variant X-67545316-TGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.231_239delGCAGCAGCA	p.Gln78_Gln80del	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.231_239delGCAGCAGCA	p.Gln78_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0976

AC:

6492

AN:

66530

Hom.:

308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0956

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0730

Gnomad ASJ

AF:

0.0921

Gnomad EAS

AF:

0.0389

Gnomad SAS

AF:

0.0670

Gnomad FIN

AF:

0.0659

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0961

GnomAD4 exome

AF:

0.0237

AC:

21760

AN:

916384

Hom.:

110

AF XY:

0.00938

AC XY:

2596

AN XY:

276646

show subpopulations

African (AFR)

AF:

0.0319

AC:

746

AN:

23351

American (AMR)

AF:

0.0250

AC:

636

AN:

25439

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

743

AN:

15703

East Asian (EAS)

AF:

0.0320

AC:

887

AN:

27742

South Asian (SAS)

AF:

0.0176

AC:

747

AN:

42325

European-Finnish (FIN)

AF:

0.0468

AC:

1634

AN:

34883

Middle Eastern (MID)

AF:

0.0398

AC:

100

AN:

2511

European-Non Finnish (NFE)

AF:

0.0212

AC:

14931

AN:

705568

Other (OTH)

AF:

0.0344

AC:

1336

AN:

38862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

1070

2140

3211

4281

5351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0976

AC:

6493

AN:

66517

Hom.:

308

Cov.:

AF XY:

0.0788

AC XY:

647

AN XY:

8215

show subpopulations

African (AFR)

AF:

0.0957

AC:

1796

AN:

18771

American (AMR)

AF:

0.0731

AC:

382

AN:

5227

Ashkenazi Jewish (ASJ)

AF:

0.0921

AC:

158

AN:

1715

East Asian (EAS)

AF:

0.0391

AC:

AN:

1841

South Asian (SAS)

AF:

0.0667

AC:

AN:

900

European-Finnish (FIN)

AF:

0.0659

AC:

133

AN:

2019

Middle Eastern (MID)

AF:

0.135

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.108

AC:

3744

AN:

34658

Other (OTH)

AF:

0.0949

AC:

AN:

811

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0457

Hom.:

237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 08, 2016

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 29, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Jul 24, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=200/0

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