X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

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.1412_1420delGCGGCGGCG(p.Gly471_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 0.0196 in 558,071 control chromosomes in the GnomAD database, including 733 homozygotes. There are 2,532 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G471G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.033 ( 77 hom., 461 hem., cov: 0)

Exomes 𝑓: 0.017 ( 656 hom. 2071 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

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-TGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 434264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1412_1420delGCGGCGGCG	p.Gly471_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.1412_1420delGCGGCGGCG	p.Gly471_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

2708

AN:

83029

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0927

Gnomad AMI

AF:

0.00195

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0108

Gnomad EAS

AF:

0.0381

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.00504

Gnomad MID

AF:

0.00513

Gnomad NFE

AF:

0.00927

Gnomad OTH

AF:

0.0217

GnomAD4 exome

AF:

0.0173

AC:

8211

AN:

475038

Hom.:

656

AF XY:

0.0176

AC XY:

2071

AN XY:

117396

show subpopulations

African (AFR)

AF:

0.104

AC:

1341

AN:

12914

American (AMR)

AF:

0.00970

AC:

AN:

8559

Ashkenazi Jewish (ASJ)

AF:

0.00829

AC:

AN:

9530

East Asian (EAS)

AF:

0.0383

AC:

536

AN:

13987

South Asian (SAS)

AF:

0.0341

AC:

496

AN:

14538

European-Finnish (FIN)

AF:

0.00485

AC:

106

AN:

21862

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

1302

European-Non Finnish (NFE)

AF:

0.0137

AC:

5090

AN:

371808

Other (OTH)

AF:

0.0226

AC:

465

AN:

20538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

154

308

461

615

769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0326

AC:

2707

AN:

83033

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

461

AN XY:

16613

show subpopulations

African (AFR)

AF:

0.0927

AC:

2005

AN:

21633

American (AMR)

AF:

0.0139

AC:

109

AN:

7817

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

AN:

2222

East Asian (EAS)

AF:

0.0374

AC:

AN:

2564

South Asian (SAS)

AF:

0.0224

AC:

AN:

1520

European-Finnish (FIN)

AF:

0.00504

AC:

AN:

2382

Middle Eastern (MID)

AF:

0.00575

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00927

AC:

400

AN:

43134

Other (OTH)

AF:

0.0233

AC:

AN:

1074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

182

272

363

454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

327

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 10, 2021

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;C1839259:Kennedy disease

Benign:1

Dec 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 21, 2020

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

1.3

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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X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

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