NM_000044.6:c.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000044.6(AR):c.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG(p.Gly461_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 0.0117 in 559,165 control chromosomes in the GnomAD database, including 430 homozygotes. There are 1,904 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 (★). Synonymous variant affecting the same amino acid position (i.e. G461G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., 94 hem., cov: 0)

Exomes 𝑓: 0.013 ( 429 hom. 1810 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -10 ACMG points.

BP6

Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1299195.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00454 (377/83056) while in subpopulation NFE AF = 0.00686 (296/43135). AF 95% confidence interval is 0.00622. There are 1 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 94 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG	p.Gly461_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.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG	p.Gly461_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

377

AN:

83052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00410

Gnomad ASJ

AF:

0.00180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00131

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00686

Gnomad OTH

AF:

0.00472

GnomAD2 exomes

AF:

0.0113

AC:

426

AN:

37570

AF XY:

0.0112

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.00574

Gnomad EAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.00581

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0130

AC:

6173

AN:

476109

Hom.:

429

AF XY:

0.0153

AC XY:

1810

AN XY:

118153

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

13217

American (AMR)

AF:

0.00804

AC:

AN:

8580

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

9546

East Asian (EAS)

AF:

0.000213

AC:

AN:

14089

South Asian (SAS)

AF:

0.00340

AC:

AN:

14715

European-Finnish (FIN)

AF:

0.00631

AC:

138

AN:

21860

Middle Eastern (MID)

AF:

0.00153

AC:

AN:

1305

European-Non Finnish (NFE)

AF:

0.0151

AC:

5612

AN:

372205

Other (OTH)

AF:

0.0110

AC:

227

AN:

20592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.697

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00454

AC:

377

AN:

83056

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

AN XY:

16626

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

21655

American (AMR)

AF:

0.00410

AC:

AN:

7814

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

2222

East Asian (EAS)

AF:

0.00

AC:

AN:

2564

South Asian (SAS)

AF:

0.00131

AC:

AN:

1522

European-Finnish (FIN)

AF:

0.00546

AC:

AN:

2381

Middle Eastern (MID)

AF:

0.00

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00686

AC:

296

AN:

43135

Other (OTH)

AF:

0.00465

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00243

Hom.:

327

Bravo

AF:

0.00411

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

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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NM_000044.6:c.1382_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

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