X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Position:

chrX-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

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

The ENST00000374690.9(AR):c.219_239delGCAGCAGCAGCAGCAGCAGCA(p.Gln74_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 0.00215 in 1,002,829 control chromosomes in the GnomAD database, including 11 homozygotes. There are 336 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 8 hom., 100 hem., cov: 0)

Exomes 𝑓: 0.0015 ( 3 hom. 236 hem. )

Consequence

AR
ENST00000374690.9 disruptive_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:

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-TGCAGCAGCAGCAGCAGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCAGCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 434262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCAGCAGCAGCAGCAGCAGCA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (754/66602) while in subpopulation AFR AF= 0.0251 (472/18788). AF 95% confidence interval is 0.0233. There are 8 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.219_239delGCAGCAGCAGCAGCAGCAGCA	p.Gln74_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.219_239delGCAGCAGCAGCAGCAGCAGCA	p.Gln74_Gln80del	disruptive_inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

751

AN:

66615

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

100

AN XY:

8237

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00233

Gnomad EAS

AF:

0.0184

Gnomad SAS

AF:

0.0121

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.00475

Gnomad OTH

AF:

0.00748

GnomAD4 exome

AF:

0.00149

AC:

1398

AN:

936227

Hom.:

AF XY:

0.000802

AC XY:

236

AN XY:

294343

show subpopulations

Gnomad4 AFR exome

AF:

0.00888

Gnomad4 AMR exome

AF:

0.00244

Gnomad4 ASJ exome

AF:

0.000677

Gnomad4 EAS exome

AF:

0.00466

Gnomad4 SAS exome

AF:

0.00253

Gnomad4 FIN exome

AF:

0.00119

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.0113

AC:

754

AN:

66602

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

100

AN XY:

8250

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00233

Gnomad4 EAS

AF:

0.0185

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00475

Gnomad4 OTH

AF:

0.00739

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	GeneDx	Jun 24, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	AR: BS1, BS2 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 22, 2016

- -

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