Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC 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.1418_1420del(p.Gly473del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 461,058 control chromosomes in the GnomAD database, including 353 homozygotes. There are 1,662 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 0.061 ( 382 hom., 692 hem., cov: 0)

Exomes 𝑓: 0.022 ( 353 hom. 1662 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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-TGGC-T is Benign according to our data. Variant chrX-67546514-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 464785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67546514-TGGC-T is described in Lovd as [Likely_benign]. Variant chrX-67546514-TGGC-T is described in Lovd as [Likely_benign]. Variant chrX-67546514-TGGC-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 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.1418_1420del	p.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.1418_1420del	p.Gly473del	inframe_deletion	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

5078

AN:

83002

Hom.:

381

Cov.:

AF XY:

0.0419

AC XY:

696

AN XY:

16614

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.00495

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0500

GnomAD4 exome

AF:

0.0218

AC:

10065

AN:

461058

Hom.:

353

AF XY:

0.0150

AC XY:

1662

AN XY:

110626

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00491

Gnomad4 EAS exome

AF:

0.0343

Gnomad4 SAS exome

AF:

0.00848

Gnomad4 FIN exome

AF:

0.0410

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0612

AC:

5078

AN:

83006

Hom.:

382

Cov.:

AF XY:

0.0416

AC XY:

692

AN XY:

16624

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.00495

Gnomad4 EAS

AF:

0.0531

Gnomad4 SAS

AF:

0.00329

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.0493

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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