Variant X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000374690.9(AR):c.228_239delGCAGCAGCAGCA(p.Gln77_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 0.0208 in 990,164 control chromosomes in the GnomAD database, including 391 homozygotes. There are 2,387 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 305 hom., 629 hem., cov: 0)

Exomes 𝑓: 0.016 ( 86 hom. 1758 hem. )

Consequence

AR
ENST00000374690.9 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.40

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 links:

AR (HGNC:):

AR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67545316-TGCAGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCAGCA-T is described in ClinVar as [Benign]. Clinvar id is 464796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCAGCAGCAGCA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.228_239delGCAGCAGCAGCA	p.Gln77_Gln80del	disruptive_inframe_deletion	1/8	ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9 linkuse as main transcript	c.228_239delGCAGCAGCAGCA	p.Gln77_Gln80del	disruptive_inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

6077

AN:

66568

Hom.:

305

Cov.:

AF XY:

0.0761

AC XY:

625

AN XY:

8218

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.0531

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.0560

Gnomad FIN

AF:

0.0588

Gnomad MID

AF:

0.0523

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0599

GnomAD4 exome

AF:

0.0157

AC:

14496

AN:

923610

Hom.:

AF XY:

0.00621

AC XY:

1758

AN XY:

282944

show subpopulations

Gnomad4 AFR exome

AF:

0.0489

Gnomad4 AMR exome

AF:

0.0207

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.00998

Gnomad4 FIN exome

AF:

0.0425

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0913

AC:

6077

AN:

66554

Hom.:

305

Cov.:

AF XY:

0.0764

AC XY:

629

AN XY:

8230

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0617

Gnomad4 ASJ

AF:

0.0531

Gnomad4 EAS

AF:

0.0288

Gnomad4 SAS

AF:

0.0556

Gnomad4 FIN

AF:

0.0588

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0616

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over