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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000044.6(AR):c.222_239dupGCAGCAGCAGCAGCAGCA(p.Gln75_Gln80dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., 54 hem., cov: 0)

Exomes 𝑓: 0.0039 ( 6 hom. 321 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:4

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 -10 ACMG points.

BP6

Variant X-67545316-T-TGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chrX-67545316-T-TGCAGCAGCAGCAGCAGCA is described in ClinVar as [Benign]. Clinvar id is 1285161.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0111 (738/66617) while in subpopulation EAS AF= 0.0206 (38/1843). AF 95% confidence interval is 0.0154. There are 13 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 link	c.222_239dupGCAGCAGCAGCAGCAGCA	p.Gln75_Gln80dup	disruptive_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 link	c.222_239dupGCAGCAGCAGCAGCAGCA	p.Gln75_Gln80dup	disruptive_inframe_insertion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

738

AN:

66630

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

AN XY:

8244

show subpopulations

Gnomad AFR

AF:

0.00618

Gnomad AMI

AF:

0.00448

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0134

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00840

Gnomad MID

AF:

0.0196

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0125

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00387

AC:

3620

AN:

934384

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

321

AN XY:

292684

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00848

Gnomad4 ASJ exome

AF:

0.00526

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.00341

Gnomad4 FIN exome

AF:

0.00920

Gnomad4 NFE exome

AF:

0.00306

Gnomad4 OTH exome

AF:

0.00501

GnomAD4 genome

AF:

0.0111

AC:

738

AN:

66617

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

AN XY:

8257

show subpopulations

Gnomad4 AFR

AF:

0.00617

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.0134

Gnomad4 EAS

AF:

0.0206

Gnomad4 SAS

AF:

0.00999

Gnomad4 FIN

AF:

0.00840

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0123

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 01, 2023

- -

AR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 05, 2021

This variant is classified as 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