Variant X-67546514-T-TGGC 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_1420dup(p.Gly473dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 541,667 control chromosomes in the GnomAD database, including 8,015 homozygotes. There are 15,605 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G456G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.26 ( 2881 hom., 2877 hem., cov: 0)

Exomes 𝑓: 0.18 ( 5134 hom. 12728 hem. )

Consequence

AR
NM_000044.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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-T-TGGC is Benign according to our data. Variant chrX-67546514-T-TGGC is described in ClinVar as [Benign]. Clinvar id is 464786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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_1420dup	p.Gly473dup	inframe_insertion	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_1420dup	p.Gly473dup	inframe_insertion	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

21722

AN:

82953

Hom.:

2882

Cov.:

AF XY:

0.173

AC XY:

2876

AN XY:

16603

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.0676

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0996

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.262

GnomAD4 exome

AF:

0.178

AC:

81685

AN:

458710

Hom.:

5134

Cov.:

AF XY:

0.119

AC XY:

12728

AN XY:

106688

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.00888

Gnomad4 SAS exome

AF:

0.0721

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.262

AC:

21718

AN:

82957

Hom.:

2881

Cov.:

AF XY:

0.173

AC XY:

2877

AN XY:

16613

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.0679

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0996

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.263

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Partial androgen insensitivity syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

African/African American population allele frequency is 24.38% (rs760580125, 767/2,962 alleles, 117 homozygotes, 127 hemizygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.3.2, this variant is classified as BENIGN. Following criteria are met: BA1 -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2019

- -

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