rs150226204

chrX-67545782-G-AchrX-67545782-G-CchrX-67545782-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_000044.6(AR):c.636G>A(p.Arg212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,210,606 control chromosomes in the GnomAD database, including 10 homozygotes. There are 1,498 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., 73 hem., cov: 22)

Exomes 𝑓: 0.0033 ( 9 hom. 1425 hem. )

Consequence

AR
NM_000044.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.672

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=-0.65).

BP7

Synonymous conserved (PhyloP=0.672 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00329 (3617/1097937) while in subpopulation SAS AF= 0.0179 (969/54085). AF 95% confidence interval is 0.017. There are 9 homozygotes in gnomad4_exome. There are 1425 alleles in male gnomad4_exome subpopulation. Median coverage is 56. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd at 73 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6 linkuse as main transcript	c.636G>A	p.Arg212=	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.636G>A	p.Arg212=	synonymous_variant	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

232

AN:

112613

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

34769

show subpopulations

Gnomad AFR

AF:

0.000548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00233

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0171

Gnomad FIN

AF:

0.000160

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00242

Gnomad OTH

AF:

0.00330

GnomAD3 exomes

AF:

0.00367

AC:

667

AN:

181906

Hom.:

AF XY:

0.00464

AC XY:

309

AN XY:

66526

show subpopulations

Gnomad AFR exome

AF:

0.000927

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000725

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00329

AC:

3617

AN:

1097937

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

1425

AN XY:

363311

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0179

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00206

AC:

232

AN:

112669

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

34835

show subpopulations

Gnomad4 AFR

AF:

0.000547

Gnomad4 AMR

AF:

0.00232

Gnomad4 ASJ

AF:

0.00263

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0171

Gnomad4 FIN

AF:

0.000160

Gnomad4 NFE

AF:

0.00242

Gnomad4 OTH

AF:

0.00326

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

Cadd

Benign

7.0

Dann

Benign

0.87

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