chrX-67546514-TGGCGGCGGCGGC-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.1409_1420delGCGGCGGCGGCG(p.Gly470_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 0.074 in 555,074 control chromosomes in the GnomAD database, including 3,978 homozygotes. There are 10,692 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 0.041 ( 80 hom., 688 hem., cov: 0)

Exomes 𝑓: 0.080 ( 3898 hom. 10004 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

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-TGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1409_1420delGCGGCGGCGGCG	p.Gly470_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.1409_1420delGCGGCGGCGGCG	p.Gly470_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

3405

AN:

83005

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0292

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0284

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0359

Gnomad NFE

AF:

0.0523

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0598

AC:

2248

AN:

37570

AF XY:

0.0514

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.0994

Gnomad NFE exome

AF:

0.0534

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0798

AC:

37682

AN:

472065

Hom.:

3898

AF XY:

0.0868

AC XY:

10004

AN XY:

115189

show subpopulations

African (AFR)

AF:

0.0258

AC:

336

AN:

13018

American (AMR)

AF:

0.0417

AC:

355

AN:

8509

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

440

AN:

9478

East Asian (EAS)

AF:

0.0660

AC:

910

AN:

13788

South Asian (SAS)

AF:

0.0651

AC:

928

AN:

14264

European-Finnish (FIN)

AF:

0.156

AC:

3355

AN:

21547

Middle Eastern (MID)

AF:

0.0594

AC:

AN:

1297

European-Non Finnish (NFE)

AF:

0.0805

AC:

29750

AN:

369781

Other (OTH)

AF:

0.0751

AC:

1531

AN:

20383

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.581

Heterozygous variant carriers

562

1124

1685

2247

2809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1024

2048

3072

4096

5120

<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:

0.0410

AC:

3403

AN:

83009

Hom.:

Cov.:

AF XY:

0.0415

AC XY:

688

AN XY:

16583

show subpopulations

African (AFR)

AF:

0.0172

AC:

373

AN:

21651

American (AMR)

AF:

0.0223

AC:

174

AN:

7815

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

AN:

2222

East Asian (EAS)

AF:

0.0403

AC:

103

AN:

2559

South Asian (SAS)

AF:

0.0243

AC:

AN:

1522

European-Finnish (FIN)

AF:

0.142

AC:

336

AN:

2368

Middle Eastern (MID)

AF:

0.0345

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.0523

AC:

2253

AN:

43110

Other (OTH)

AF:

0.0400

AC:

AN:

1075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0324

Hom.:

327

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 19, 2020

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

- -

not provided

Benign:2

Oct 03, 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

- -

Nov 12, 2019

GeneDx

Significance: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

- -

Androgen resistance syndrome

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

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