Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000044.6(AR):c.1415_1420delGCGGCG(p.Gly472_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 0.0114 in 557,735 control chromosomes in the GnomAD database, including 418 homozygotes. There are 1,145 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 169 hom., 408 hem., cov: 0)

Exomes 𝑓: 0.0070 ( 249 hom. 737 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.29

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-67546514-TGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 434260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGCGGC-T is described in Lovd as [Likely_benign]. Variant chrX-67546514-TGGCGGC-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 link	c.1415_1420delGCGGCG	p.Gly472_Gly473del	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 link	c.1415_1420delGCGGCG	p.Gly472_Gly473del	disruptive_inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

3014

AN:

83027

Hom.:

169

Cov.:

AF XY:

0.0245

AC XY:

407

AN XY:

16611

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.000450

Gnomad EAS

AF:

0.00505

Gnomad SAS

AF:

0.00720

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00513

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.0255

GnomAD4 exome

AF:

0.00700

AC:

3325

AN:

474704

Hom.:

249

AF XY:

0.00628

AC XY:

737

AN XY:

117274

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.00596

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00695

Gnomad4 SAS exome

AF:

0.00743

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.00298

Gnomad4 OTH exome

AF:

0.0151

GnomAD4 genome

AF:

0.0364

AC:

3019

AN:

83031

Hom.:

169

Cov.:

AF XY:

0.0245

AC XY:

408

AN XY:

16621

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.000450

Gnomad4 EAS

AF:

0.00507

Gnomad4 SAS

AF:

0.00723

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.0251

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 26, 2017

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 13, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2019

- -

AR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2019

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