X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000044.6(AR):c.1403_1420delGCGGCGGCGGCGGCGGCG(p.Gly468_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 0.0251 in 558,345 control chromosomes in the GnomAD database, including 1,198 homozygotes. There are 3,999 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 Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 7 hom., 172 hem., cov: 0)

Exomes 𝑓: 0.028 ( 1191 hom. 3827 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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-TGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1168910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.011 (912/83045) while in subpopulation NFE AF = 0.0142 (612/43129). AF 95% confidence interval is 0.0133. There are 7 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1403_1420delGCGGCGGCGGCGGCGGCG	p.Gly468_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.1403_1420delGCGGCGGCGGCGGCGGCG	p.Gly468_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

912

AN:

83041

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00499

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.00666

Gnomad ASJ

AF:

0.00945

Gnomad EAS

AF:

0.00272

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.00672

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00660

GnomAD2 exomes

AF:

0.0287

AC:

1079

AN:

37570

AF XY:

0.0225

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.0447

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.00673

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0284

GnomAD4 exome

AF:

0.0276

AC:

13127

AN:

475300

Hom.:

1191

AF XY:

0.0325

AC XY:

3827

AN XY:

117708

show subpopulations

African (AFR)

AF:

0.00793

AC:

104

AN:

13120

American (AMR)

AF:

0.0270

AC:

231

AN:

8557

Ashkenazi Jewish (ASJ)

AF:

0.0238

AC:

227

AN:

9527

East Asian (EAS)

AF:

0.00633

AC:

AN:

13901

South Asian (SAS)

AF:

0.0455

AC:

667

AN:

14650

European-Finnish (FIN)

AF:

0.0121

AC:

265

AN:

21836

Middle Eastern (MID)

AF:

0.00613

AC:

AN:

1304

European-Non Finnish (NFE)

AF:

0.0297

AC:

11061

AN:

371841

Other (OTH)

AF:

0.0231

AC:

476

AN:

20564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.601

Heterozygous variant carriers

199

398

596

795

994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0110

AC:

912

AN:

83045

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

172

AN XY:

16615

show subpopulations

African (AFR)

AF:

0.00499

AC:

108

AN:

21653

American (AMR)

AF:

0.00665

AC:

AN:

7815

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

AN:

2222

East Asian (EAS)

AF:

0.00273

AC:

AN:

2563

South Asian (SAS)

AF:

0.0131

AC:

AN:

1522

European-Finnish (FIN)

AF:

0.00672

AC:

AN:

2382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.0142

AC:

612

AN:

43129

Other (OTH)

AF:

0.00651

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0131

Hom.:

327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AR: BS1, BS2 -

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-TGGCGGCGGCGGCGGCGGCGGCGGC

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