NM_000044.6:c.1418_1420delGCG

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.1418_1420delGCG(p.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 0.0218 in 461,058 control chromosomes in the GnomAD database, including 353 homozygotes. There are 1,662 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G473G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.061 ( 382 hom., 692 hem., cov: 0)

Exomes 𝑓: 0.022 ( 353 hom. 1662 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely 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-TGGC-T is Benign according to our data. Variant chrX-67546514-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1418_1420delGCG	p.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.1418_1420delGCG	p.Gly473del	disruptive_inframe_deletion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

5078

AN:

83002

Hom.:

381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.00495

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0500

GnomAD4 exome

AF:

0.0218

AC:

10065

AN:

461058

Hom.:

353

AF XY:

0.0150

AC XY:

1662

AN XY:

110626

show subpopulations

African (AFR)

AF:

0.140

AC:

1808

AN:

12877

American (AMR)

AF:

0.0106

AC:

AN:

8416

Ashkenazi Jewish (ASJ)

AF:

0.00491

AC:

AN:

9362

East Asian (EAS)

AF:

0.0343

AC:

464

AN:

13529

South Asian (SAS)

AF:

0.00848

AC:

121

AN:

14264

European-Finnish (FIN)

AF:

0.0410

AC:

867

AN:

21139

Middle Eastern (MID)

AF:

0.0197

AC:

AN:

1269

European-Non Finnish (NFE)

AF:

0.0171

AC:

6161

AN:

360239

Other (OTH)

AF:

0.0242

AC:

484

AN:

19963

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

334

668

1003

1337

1671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0612

AC:

5078

AN:

83006

Hom.:

382

Cov.:

AF XY:

0.0416

AC XY:

692

AN XY:

16624

show subpopulations

African (AFR)

AF:

0.191

AC:

4125

AN:

21616

American (AMR)

AF:

0.0242

AC:

189

AN:

7810

Ashkenazi Jewish (ASJ)

AF:

0.00495

AC:

AN:

2221

East Asian (EAS)

AF:

0.0531

AC:

136

AN:

2563

South Asian (SAS)

AF:

0.00329

AC:

AN:

1521

European-Finnish (FIN)

AF:

0.0273

AC:

AN:

2378

Middle Eastern (MID)

AF:

0.0287

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.0113

AC:

489

AN:

43134

Other (OTH)

AF:

0.0493

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

162

323

485

646

808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00701

Hom.:

327

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Nov 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 16, 2019

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

=75/25

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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NM_000044.6:c.1418_1420delGCG

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