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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000044.6(AR):c.228_239dup(p.Gln77_Gln80dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 995,294 control chromosomes in the GnomAD database, including 87 homozygotes. There are 759 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 73 hom., 161 hem., cov: 0)

Exomes 𝑓: 0.012 ( 14 hom. 598 hem. )

Consequence

AR
NM_000044.6 inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.337

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67545316-T-TGCAGCAGCAGCA is Benign according to our data. Variant chrX-67545316-T-TGCAGCAGCAGCA is described in ClinVar as [Benign]. Clinvar id is 1168151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.035 (2331/66600) while in subpopulation EAS AF= 0.0582 (107/1840). AF 95% confidence interval is 0.0492. There are 73 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 73 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.228_239dup	p.Gln77_Gln80dup	inframe_insertion	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_239dup	p.Gln77_Gln80dup	inframe_insertion	1/8	1	NM_000044.6	ENSP00000363822	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

2332

AN:

66613

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

161

AN XY:

8233

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00897

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.0321

Gnomad EAS

AF:

0.0584

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.0469

Gnomad MID

AF:

0.0261

Gnomad NFE

AF:

0.0412

Gnomad OTH

AF:

0.0374

GnomAD4 exome

AF:

0.0119

AC:

11056

AN:

928694

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

598

AN XY:

287162

show subpopulations

Gnomad4 AFR exome

AF:

0.00634

Gnomad4 AMR exome

AF:

0.0231

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0411

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0394

Gnomad4 NFE exome

AF:

0.00868

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0350

AC:

2331

AN:

66600

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

161

AN XY:

8246

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0321

Gnomad4 EAS

AF:

0.0582

Gnomad4 SAS

AF:

0.0333

Gnomad4 FIN

AF:

0.0469

Gnomad4 NFE

AF:

0.0412

Gnomad4 OTH

AF:

0.0369

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2015

- -

AR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 17, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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