Variant X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA 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.222_239del(p.Gln75_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,001,605 control chromosomes in the GnomAD database, including 38 homozygotes. There are 591 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 35 hom., 185 hem., cov: 0)

Exomes 𝑓: 0.0028 ( 3 hom. 406 hem. )

Consequence

AR
NM_000044.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67545316-TGCAGCAGCAGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 418806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0195 (1300/66602) while in subpopulation AFR AF= 0.0385 (723/18788). AF 95% confidence interval is 0.0362. There are 35 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.222_239del	p.Gln75_Gln80del	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.222_239del	p.Gln75_Gln80del	inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

1299

AN:

66615

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

184

AN XY:

8235

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0134

Gnomad EAS

AF:

0.00487

Gnomad SAS

AF:

0.00768

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.00913

Gnomad OTH

AF:

0.0137

GnomAD4 exome

AF:

0.00277

AC:

2591

AN:

935003

Hom.:

AF XY:

0.00138

AC XY:

406

AN XY:

293243

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.00368

Gnomad4 SAS exome

AF:

0.00223

Gnomad4 FIN exome

AF:

0.00750

Gnomad4 NFE exome

AF:

0.00190

Gnomad4 OTH exome

AF:

0.00458

GnomAD4 genome

AF:

0.0195

AC:

1300

AN:

66602

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

185

AN XY:

8248

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.0134

Gnomad4 EAS

AF:

0.00489

Gnomad4 SAS

AF:

0.00777

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00913

Gnomad4 OTH

AF:

0.0148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	AR: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2021	This variant is associated with the following publications: (PMID: 15242343) -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 09, 2017

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 24, 2023

- -

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