Variant rs6152 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000044.6(AR):c.639G>A(p.Glu213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,209,546 control chromosomes in the GnomAD database, including 16,446 homozygotes. There are 62,319 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 4860 hom., 8618 hem., cov: 23)

Exomes 𝑓: 0.15 ( 11586 hom. 53701 hem. )

Consequence

AR
NM_000044.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.62

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=1.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 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.639G>A	p.Glu213=	synonymous_variant	1/8	ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9 linkuse as main transcript	c.639G>A	p.Glu213=	synonymous_variant	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

30456

AN:

111940

Hom.:

4860

Cov.:

AF XY:

0.251

AC XY:

8583

AN XY:

34128

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00169

Gnomad SAS

AF:

0.0799

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.238

GnomAD3 exomes

AF:

0.152

AC:

27505

AN:

181185

Hom.:

2808

AF XY:

0.135

AC XY:

8911

AN XY:

65899

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.0765

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.000724

Gnomad SAS exome

AF:

0.0886

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.152

AC:

166871

AN:

1097551

Hom.:

11586

Cov.:

AF XY:

0.148

AC XY:

53701

AN XY:

362953

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.0851

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.000629

Gnomad4 SAS exome

AF:

0.0893

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.272

AC:

30495

AN:

111995

Hom.:

4860

Cov.:

AF XY:

0.252

AC XY:

8618

AN XY:

34193

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.00170

Gnomad4 SAS

AF:

0.0802

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.192

Hom.:

2201

Bravo

AF:

0.285

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 25241384, 19167832, 15824176, 11231320) -

Androgen resistance syndrome

Benign:1

Benign, no assertion criteria provided

literature only

GeneReviews

Jul 10, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

7.3

Dann

Benign

0.83

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