X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

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.225_239delGCAGCAGCAGCAGCA(p.Gln76_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 0.00777 in 997,172 control chromosomes in the GnomAD database, including 184 homozygotes. There are 1,000 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 (★★).

Frequency

Genomes: 𝑓 0.050 ( 169 hom., 403 hem., cov: 0)

Exomes 𝑓: 0.0048 ( 15 hom. 597 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

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:

Genome browser will be placed here

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-TGCAGCAGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCAGCAGCA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.225_239delGCAGCAGCAGCAGCA	p.Gln76_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.225_239delGCAGCAGCAGCAGCA	p.Gln76_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

3322

AN:

66603

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0307

Gnomad FIN

AF:

0.00346

Gnomad MID

AF:

0.0131

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0549

GnomAD4 exome

AF:

0.00476

AC:

4426

AN:

930582

Hom.:

AF XY:

0.00206

AC XY:

597

AN XY:

289264

show subpopulations

African (AFR)

AF:

0.0403

AC:

931

AN:

23129

American (AMR)

AF:

0.00885

AC:

227

AN:

25663

Ashkenazi Jewish (ASJ)

AF:

0.00988

AC:

159

AN:

16091

East Asian (EAS)

AF:

0.0115

AC:

324

AN:

28174

South Asian (SAS)

AF:

0.00807

AC:

358

AN:

44366

European-Finnish (FIN)

AF:

0.00263

AC:

AN:

35795

Middle Eastern (MID)

AF:

0.00742

AC:

AN:

2560

European-Non Finnish (NFE)

AF:

0.00263

AC:

1882

AN:

715256

Other (OTH)

AF:

0.0109

AC:

432

AN:

39548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

212

425

637

850

1062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.0499

AC:

3324

AN:

66590

Hom.:

169

Cov.:

AF XY:

0.0489

AC XY:

403

AN XY:

8238

show subpopulations

African (AFR)

AF:

0.135

AC:

2540

AN:

18774

American (AMR)

AF:

0.0309

AC:

162

AN:

5235

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

1714

East Asian (EAS)

AF:

0.0179

AC:

AN:

1843

South Asian (SAS)

AF:

0.0300

AC:

AN:

901

European-Finnish (FIN)

AF:

0.00346

AC:

AN:

2025

Middle Eastern (MID)

AF:

0.0150

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.0136

AC:

473

AN:

34708

Other (OTH)

AF:

0.0543

AC:

AN:

811

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

119

238

358

477

596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.000137

Hom.:

237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 13, 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Prostate cancer;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked

Benign:1

Jul 06, 2021

Fulgent Genetics, Fulgent Genetics

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

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

=195/5

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