NM_000044.6:c.1400_1420delGCGGCGGCGGCGGCGGCGGCG

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.1400_1420delGCGGCGGCGGCGGCGGCGGCG(p.Gly467_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 0.0128 in 558,215 control chromosomes in the GnomAD database, including 548 homozygotes. There are 2,000 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G467G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., 118 hem., cov: 0)

Exomes 𝑓: 0.014 ( 545 hom. 1882 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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-TGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1166508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00615 (511/83056) while in subpopulation AMR AF = 0.00832 (65/7816). AF 95% confidence interval is 0.00669. There are 3 homozygotes in GnomAd4. There are 118 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1400_1420delGCGGCGGCGGCGGCGGCGGCG	p.Gly467_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.1400_1420delGCGGCGGCGGCGGCGGCGGCG	p.Gly467_Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

506

AN:

83052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00769

Gnomad ASJ

AF:

0.000450

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00196

Gnomad FIN

AF:

0.00210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.00189

GnomAD2 exomes

AF:

0.0121

AC:

455

AN:

37570

AF XY:

0.00840

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.000319

Gnomad EAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0140

AC:

6641

AN:

475159

Hom.:

545

AF XY:

0.0160

AC XY:

1882

AN XY:

117809

show subpopulations

African (AFR)

AF:

0.0105

AC:

138

AN:

13200

American (AMR)

AF:

0.0166

AC:

142

AN:

8537

Ashkenazi Jewish (ASJ)

AF:

0.000210

AC:

AN:

9506

East Asian (EAS)

AF:

0.00206

AC:

AN:

14084

South Asian (SAS)

AF:

0.00999

AC:

146

AN:

14618

European-Finnish (FIN)

AF:

0.00243

AC:

AN:

21829

Middle Eastern (MID)

AF:

0.00460

AC:

AN:

1304

European-Non Finnish (NFE)

AF:

0.0159

AC:

5922

AN:

371518

Other (OTH)

AF:

0.00987

AC:

203

AN:

20563

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.622

Heterozygous variant carriers

105

210

314

419

524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00615

AC:

511

AN:

83056

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

118

AN XY:

16626

show subpopulations

African (AFR)

AF:

0.00684

AC:

148

AN:

21653

American (AMR)

AF:

0.00832

AC:

AN:

7816

Ashkenazi Jewish (ASJ)

AF:

0.000450

AC:

AN:

2222

East Asian (EAS)

AF:

0.00156

AC:

AN:

2564

South Asian (SAS)

AF:

0.00197

AC:

AN:

1522

European-Finnish (FIN)

AF:

0.00210

AC:

AN:

2382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00656

AC:

283

AN:

43134

Other (OTH)

AF:

0.00186

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00310

Hom.:

327

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 09, 2018

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 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

=200/0

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.1400_1420delGCGGCGGCGGCGGCGGCGGCG

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