Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC 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.1409_1420del(p.Gly470_Gly473del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 555,074 control chromosomes in the GnomAD database, including 3,978 homozygotes. There are 10,692 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G457G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.041 ( 80 hom., 688 hem., cov: 0)

Exomes 𝑓: 0.080 ( 3898 hom. 10004 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: 1.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67546514-TGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGCGGCGGCGGC-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6 linkuse as main transcript	c.1409_1420del	p.Gly470_Gly473del	inframe_deletion	1/8	ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9 linkuse as main transcript	c.1409_1420del	p.Gly470_Gly473del	inframe_deletion	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

3405

AN:

83005

Hom.:

Cov.:

AF XY:

0.0416

AC XY:

689

AN XY:

16573

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0292

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0284

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0359

Gnomad NFE

AF:

0.0523

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0598

AC:

2248

AN:

37570

Hom.:

474

AF XY:

0.0514

AC XY:

667

AN XY:

12980

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.0994

Gnomad NFE exome

AF:

0.0534

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0798

AC:

37682

AN:

472065

Hom.:

3898

AF XY:

0.0868

AC XY:

10004

AN XY:

115189

show subpopulations

Gnomad4 AFR exome

AF:

0.0258

Gnomad4 AMR exome

AF:

0.0417

Gnomad4 ASJ exome

AF:

0.0464

Gnomad4 EAS exome

AF:

0.0660

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.0805

Gnomad4 OTH exome

AF:

0.0751

GnomAD4 genome

AF:

0.0410

AC:

3403

AN:

83009

Hom.:

Cov.:

AF XY:

0.0415

AC XY:

688

AN XY:

16583

show subpopulations

Gnomad4 AFR

AF:

0.0172

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0284

Gnomad4 EAS

AF:

0.0403

Gnomad4 SAS

AF:

0.0243

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.0523

Gnomad4 OTH

AF:

0.0400

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

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 19, 2020

- -

Androgen resistance syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 18, 2021

- -

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