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

Variant summary

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

The ENST00000374690.9(AR):c.216_239delGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln73_Gln80del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,003,104 control chromosomes in the GnomAD database, including 19 homozygotes. There are 468 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., 134 hem., cov: 0)

Exomes 𝑓: 0.0016 ( 4 hom. 334 hem. )

Consequence

AR
ENST00000374690.9 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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:

AR (HGNC:):

AR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCAGCAGCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 533380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCAGCAGCA-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (812/66610) while in subpopulation AFR AF= 0.0286 (538/18795). AF 95% confidence interval is 0.0266. There are 15 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.216_239delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln73_Gln80del	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 linkuse as main transcript	c.216_239delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln73_Gln80del	disruptive_inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

813

AN:

66623

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

134

AN XY:

8239

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00466

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.000988

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00493

Gnomad OTH

AF:

0.0150

GnomAD4 exome

AF:

0.00159

AC:

1489

AN:

936494

Hom.:

AF XY:

0.00113

AC XY:

334

AN XY:

294584

show subpopulations

Gnomad4 AFR exome

AF:

0.00739

Gnomad4 AMR exome

AF:

0.00240

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00102

Gnomad4 SAS exome

AF:

0.00623

Gnomad4 FIN exome

AF:

0.00138

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.00336

GnomAD4 genome

AF:

0.0122

AC:

812

AN:

66610

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

134

AN XY:

8252

show subpopulations

Gnomad4 AFR

AF:

0.0286

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00466

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.0200

Gnomad4 FIN

AF:

0.000988

Gnomad4 NFE

AF:

0.00493

Gnomad4 OTH

AF:

0.0148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	AR: BS1, BS2 -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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