NM_000044.6:c.237_239delGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000044.6(AR):c.237_239delGCA(p.Gln80del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 981,829 control chromosomes in the GnomAD database, including 1,031 homozygotes. There are 4,595 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 753 hom., 775 hem., cov: 0)

Exomes 𝑓: 0.042 ( 278 hom. 3820 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.40

Publications

10 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, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae)
Kennedy disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
partial androgen insensitivity syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000044.6

BP6

Variant X-67545316-TGCA-T is Benign according to our data. Variant chrX-67545316-TGCA-T is described in ClinVar as Benign. ClinVar VariationId is 464798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000044.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	NM_000044.6	MANE Select	c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 8	NP_000035.2
AR	NM_001348063.1		c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 4	NP_001334992.1	Q9NUA2
AR	NM_001348061.1		c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 4	NP_001334990.1	Q9NUA2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	ENST00000374690.9	TSL:1 MANE Select	c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000363822.3	P10275-1
AR	ENST00000396044.8	TSL:1	c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 5	ENSP00000379359.3	F5GZG9
AR	ENST00000504326.5	TSL:1	c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	Exon 1 of 4	ENSP00000421155.1	P10275-3

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

10163

AN:

66458

Hom.:

753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.144

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.0417

AC:

38184

AN:

915384

Hom.:

278

AF XY:

0.0139

AC XY:

3820

AN XY:

274494

show subpopulations

African (AFR)

AF:

0.0376

AC:

878

AN:

23352

American (AMR)

AF:

0.0519

AC:

1304

AN:

25112

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

764

AN:

15776

East Asian (EAS)

AF:

0.0844

AC:

2272

AN:

26920

South Asian (SAS)

AF:

0.0296

AC:

1260

AN:

42619

European-Finnish (FIN)

AF:

0.120

AC:

4186

AN:

34751

Middle Eastern (MID)

AF:

0.0562

AC:

140

AN:

2490

European-Non Finnish (NFE)

AF:

0.0356

AC:

25151

AN:

705602

Other (OTH)

AF:

0.0575

AC:

2229

AN:

38762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1815

3631

5446

7262

9077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.153

AC:

10160

AN:

66445

Hom.:

753

Cov.:

AF XY:

0.0940

AC XY:

775

AN XY:

8241

show subpopulations

African (AFR)

AF:

0.109

AC:

2053

AN:

18756

American (AMR)

AF:

0.145

AC:

756

AN:

5217

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

200

AN:

1711

East Asian (EAS)

AF:

0.115

AC:

212

AN:

1842

South Asian (SAS)

AF:

0.101

AC:

AN:

899

European-Finnish (FIN)

AF:

0.159

AC:

320

AN:

2013

Middle Eastern (MID)

AF:

0.158

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.183

AC:

6328

AN:

34622

Other (OTH)

AF:

0.161

AC:

130

AN:

808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

356

711

1067

1422

1778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0722

Hom.:

237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Prostate cancer;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked (1)

Androgen resistance syndrome;C1839259:Kennedy disease (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=77/23

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over